行政院國家科學委員會專題研究計畫 成果報告
台灣地區登革病毒感染的分子流行病學與化學激素的角色
(2/2)
計畫類別： 個別型計畫
計畫編號： NSC91-2320-B-002-081-
執行期間： 91 年 08 月 01 日至 92 年 07 月 31 日
執行單位： 國立臺灣大學公共衛生學院流行病學研究所
計畫主持人： 金傳春
計畫參與人員： 沈倬光,王慧婷,趙黛瑜
報告類型： 完整報告
報告附件： 國外研究心得報告
處理方式： 本計畫可公開查詢
中 華 民 國 93 年 3 月 29 日
中文摘要
嚴重臨床症狀的登革出血熱與較為輕微症狀的登革熱之免疫致病機制差異
至今尚未被釐清。本研究目的是探討登革出血熱與登革熱病人致病過程中的 3
種人類化學激素(RANTES, Mig, MIP-1α chemokines)分泌變化是否有差異性存
在，且此差異是否與登革病患臨床狀的嚴重度有所關連。
研究群是以 2002 年月至 2003 年 3 月高屏地區通報登革熱病例為研究對
象，並經由台灣疾病管制局確認登革出血熱病例共 23 名與登革熱病例共 77
名，另取 46 名健康對照組作為比較,進行抽血，以流式細胞儀分析細胞表面人
類化學激素受體及酵素免疫試劑測人類化學激素分泌量，並請醫護人員進行問
卷訪談並追蹤症狀。
結果發現：（1）登革熱病患體內 CD4/CD3+T 細胞比值顯著低於健康對照組
（33.19±2.21 vs 40.13±15.94, p=0.03）；（2）登革出血熱與登革熱確定病例
的人類化學激素如
RANTES（各為 13.69+3.46 ng/ml 與 19.56+2.74 ng/ml,
p=0.14）、Mig（各為 653.45+ 85.89 pg/ml 與 664.63+ 59.60 pg/ml, p=0.23）均
比健康人有顯著較高的分泌量，但此兩種登革病人的 MIP-1a 分泌量(各為
26.99+ 11.56pg/ml 與 38.59+ 9.86pg/ml)卻較健康人為低（92.47±13.55 pg/ml,
p<0.01）
；
（3）不同的化學激素在病程之動態分泌量有所不同,人類化學激素如
Mig 的分泌量在登革出血熱/登革熱病例急性期高於恢復期，相對地 RANTES
分泌量在登革出血熱/登革熱病例急性期卻低於恢復期。
本研究初步結果推論登革熱出血熱/登革熱病患其人類化學激素分泌變化
有差異性存在，登革出血熱病患體內人類化學激素
Mig 在發燒後頭三天(感
染急性期)有較高的分泌, 可能加速吸引帶有
CXCR3 之 T 細胞至受感染部
位，且因
RANTES 有持續性的分泌,由此三者的協同作用,會增進 CD8
+T 細
胞中
CCR5 的表現量，進而引起相關的細胞受到傷害，結果造成病人的嚴重
出血。未來實有必要再更急性早期採集登革病人血液檢體,以整合病毒量.免
疫活化標誌與血液動態指標,以徹底明瞭登革出血熱病人的免疫致病機轉.
關鍵字: 登革熱、人類化學激素、人類化學激素受體、登革病毒免疫、免疫流行
病學
Abstract
Mechanism of immunopathogenesis in leading to dengue hemorrhagic fever (DHF)
versus mild form of dengue fever (DF) during the same epidemic has not been fully
understood. The specific aims of this study were to determine whether there are
differences in the levels of chemokines (RANTES, Mig and MIP-1a ) associated with
hemorrhage between DHF and DF patients or clinical complications.
A prospective cohort study recruited 23 DHF and 77 DF patients caused by dengue
virus serotype 2 plus 46 healthy donors from Aug. 2 to Mar. 31, 2003 in Kaohsiung
and Pingtung. Levels of RANTES, Mig, MIP-1a were measured in serum samples
collected at both the first visit and subsequent repeated visits. Mann-Whitney U and
Spearman correlation test were used to compare the relationship between above each
chemokine and clinical status of DF vs DHF or hemodynamic/ biochemical laboratory
results, and their kinetic changes at different time points after the onset of fever,
respectively.
Ratios of CD4/CD3+T cells in DF patients was lower significantly compared to
healthy controls (DF patients: 33.19+ 2.21 vs healthy controls: 40.13 + 15.94, P=0.03).
There were higher serum levels of RANTES ( DHF: 13.69+3.46 vs DF: 19.56+2.74,
P=0.14), Mig (DHF: 653.45+ 85.89 vs DF: 664.63+ 59.60, P=0.23) and lower levels
of MIP-1a (DHF: 26.99+ 11.56 vs DF: 38.59+ 9.86, P=0.56). However, serum levels
of RANTES, Mig were significantly higher than healthy controls (P<0.05), whereas
levels of MIP-1a in dengue patients were significantly lower than compared to healthy
controls (P<0.05). The serum levels of chemokine were also compared after fever
onset. Levels of Mig in DHF and DF patients after fever onset 7 days were higher
≦
than that after fever onset >7 days. In contrast, levels of RANTES in DHF and DF
patients were lower after fever onset 7 days than that after fever onset >7 days.
≦
.
In conclusion, the serum chemokine kinetic patterns of DHF were different from
DF patients. These effects may lead to infected cells damages and then cause
hemorrhage. A closer examination of the production of these chemokines and the
activation of dengue virus infected target cells in the early phase of dengue virus
infection is warranted to attain a better understanding of immunopathgenesis of DHF.
Keywords: Dengue hemorrhagic fever, Innate Immunity, Immunological Responses,
Introduction and Literature Review
Understanding on the pathogenesis of DHF/DSS provides more insights to prevent
severe dengue cases and decreasing case fatality rate. Exaggerated cellular immune
responses to dengue virus infection which are driven by cross-reactive memory T
lymphocytes may result in increasing disease severity and DHF【Rothman et al.,
1999】. Dysregulation of certain innate and bystander immune activation might play
an important role in exacerbating disease progression during dengue virus infection.
Chemokines are involved in the recruitment of leukocytes to sites of infection via
a cascade of coordinated events. Chemokines are synthesized and secreted by
macrophages/monocytes, endothelial cells, fibroblasts, epithelial cells, and
neutrophils during inflammation including RANTES, MIP-1α, IP-10, and Mig and
function to induce leukocytes adherence to vascular endothelium and extravasation
into tissues. Furthermore, chemokines might play an important role in the
pathogenesis of dengue virus infection, because levels of certain chemokines , such as
IL-8 and RANTES, were elevated during dengue virus infection in vitro or in vivo
【Lin et al., 2000; King et al., 2002】.
However, other chemokines in the immunopathogenesis of dengue virus infection
have not been explored. In our present study, we attempted to obtain an integrated
view of the chemokine-cehmokine receptors after dengue virus infection by obtaining
repeated measurements of blood samples from patients of dengue hemorrhagic fever
and dengue fever during the largest epidemic of DHF in Taiwan in 2002’ and
comparing the similarities and differences in quantitative kinetic changes between
these two groups of dengue patients with different clinical severity.
MATERIALS and METHODS
A. Study Areas
Study areas include past and present epidemic areas of dengue. Past
epidemic areas were (1) Kaohsiung County and City, and (2) Pingtung County
and City. Physicians/nurses working at the sentinel hospitals/clinics in these
study areas collected blood samples for this study.
B. Study Populations
The study subjects include confirmed DF, confirmed DHF/DSS cases, and the
healthy controls. The diagnosis of dengue infection was confirmed by the Center of
Disease Control (CDC), Taiwan. Both dengue-consensus and type-specific primers for
reverse-transcriptase polymerase chain reaction (RT-PCR). (>10 PFU is detectable)
and serologic tests (dengue-specific IgM seropositive or 4-fold serotiter rise but
Japanese-specific IgM seronegative) are used for confirming dengue virus will be
conducted mainly in our lab at National Taiwan University (NTU) to minimize false
results. Healthy donors chose people who lived in the area of Taipei City without
indigenous dengue cases reported.Patients with serotype one, three, and four
confirmed from laboratory tests (PCR and antibody tests) are analysis separately.
C. Clinical Diagnosis of Dengue Fever and Dengue Hemorrhagic Fever/Dengue
Shock Syndrome
Clinical diagnosis of dengue fever and dengue hemorrhagic fever/dengue
shock syndrome was defined according to the criteria of the World Health
Organization. All patient with dengue hemorrhagic fever had thrombocytopenia
(<100,000/mm
3) and hemocencentration ( hematocrit > 20% of recovery value)
or > 1mm of pleural effusion detected on the right lateral chest radiograph.
D. Interview and Questionnaire
A personal interview based on standardized questionnaire will be conducted by
nosocomial infection control nurses who are well-trained on interview techniques and
questionnaire details in their hospitals. Questions are briefly listed as following:
1. Demographic Data: Gender, age, birth date and living areas
hepatitis, diabetes are included. In addition, History of dengue for case
and his/her family members, relatives, neighbors, coworkers and
classmates are recorded.
3. Date of Onset: Including the first date of fever, and other symptoms
and signs of dengue.
4. Clinical complication: To record patients who develop clinical
complications such as ascites, pleural effusion, or petechiae during their
hospital stay.
5. Clinical hematologic data: WBCs, lymphocyte, hematocrit, platelet,
ALT, AST
6. Risk Factors: Travel history to those dengue hyper-endemic or
epidemic areas during the incubation time.
E. Collection of Blood Samples
Two blood samples will be collected from confirmed dengue cases using
vacuum syringes with anti-coagulant (EDTA) for flow cytometry and without
anti-coagulant for chemokine tests. Serum collected through day 7 after fever
onset are referred to as acute-phase samples. Convalescent serum refer to
specimens collected 8 days or more after fever onset. The samples will be
immediately placed on ice and transported to our laboratory in the ice-filled
bottle/box by express service.
F. Laboratory Methods
1. Flow Cytometry
Using whole blood samples and stained with florescence conjugated with cell
surface CD molecule antibody right after those samples’ arrival to quantitate
subpopulations of T cells, including CD45RO, CD62L. CCR5 and CXCR3 stained to
detect chemokine receptor expression.
2. CD Masker Staining
Collect blood especially by venipuncture into a sterile K3 EDTA VACUTAINER
blood collection tube. Follow the collection tube manufacturer’s guidelines for the
minimun volume of blood to be collected. Store anticoagulated blood at room temp
(20
oto 25
oC) until ready for staining and lysing. Refer to the appropriate package
insert for storage restrictions prior to staining.
Analyze on the FACS brand flow cytometer. Mix samples thoroughly before
acquisition. Refer to the appropriate package insert for storage restrictions prior to
analysis.
3. Quantitation of Chmeokines
Serum levels of RANTES (cat.no.DRN00), IP-10 (cat.no.DIP100), Mig (cat.no.
DCX900), MIP-1α (cat.no. DMA00) were measured by use of commercial ELISA
kits (Quantikine, R&D System). As described by the manufacturer, lower detection
limits for the assays are 8 pg/ml for RANTES, 1.67 pg/ml for IP-10, 3.84 pg/ml for
Mig, 10 pg/ml for MIP-1α.
G. Statistical Data Analysis
All information was compiled with EXCELL software (Office 2000, Microsoft)
and analyzed by The Statistic Analysis Software 8.2 (SAS, Institute, Inc). Serum
chemokine levels were compared by use of the Kruskall-Wallis test, a nonparametric
analysis of variance. When the test revealed significant differences between the study
groups, 2-group comparisons were done with the Mann-Whitney U test. The
Wilcoxon signed rank test was used for comparison of paired samples from each
individual. Correlations between variables were evaluated with Spearman correlation
test. P < 0.05 was considered a statistically significance difference between groups.
Results
Serum samples from 138 individuals were selected for analysis and were
categorized into the following groups: 34 DHF patients , 90 DF patients , and 14
healthy controls (table 2). Between onset of fever and days of collecting serum
samples varied between the groups, but the differences were not statistically
significant (table 2). We can find that DHF patients were older(50.59±13.78), had
more underlying disease of diabetes(29.41%) and collected more earlier whole blood
samples at less than 7 days after onset of fever(58.82%) .
After fever onset ≦7 days represented the acute or early phase of illness, a time
when ongoing inflammatory responses were likely to be at a maximum. After fever
onset ＞7 days represented likely a late or convalescent phase of illness, a time when
inflammation would be expected to be resolving or be in a preterminal stage in those
who succumbed to disease.
A. Fundamental immunological markers in patients of DF versus DHF
There were differences in the ratios of CD4+T/CD3+T cells (DHF:36.34+ 5.18;
DF:33.19 + 2.21 ) and CD8+T/CD3+T cells (DHF: 27.34 + 3.60; DF: 30.20+ 1.89 ) in
DHF and DF patients compared with Healthy controls ( CD4+T/CD3+T cells: 40.13 +
2.35; CD8+T/CD3+T cells: 31.88 + 1.62; Table 3).
The significant differences only existed in the ratio of CD4+T/CD3+T cells in
DF patients compared with healthy controls (P=0.03). There were differences in the
CD3+ T cells absolute numbers in DHF (3140.6±907.8)and DF(3143.6±400.93)
patients compared to healthy controls(4567.4±482.85). The CD3+ T cells absolute
numbers were significant differences were present in DF and healthy controls
(p=0.02). There were differences in the CD4+ T cells and CD8+ T cells absolute
numbers in DHF (CD4+ T cells: 1959.9±431.09; CD8+T cells: 1933.2±457.2)and
DF(CD4+ T cells: 1869.8±157.16; CD8+T cells: 1899.3±226.93) patients compared
to healthy controls(CD4+ T cells: 2582.9±208.7; CD8+T cells: 2085.8±202.61).
Similar significant differences were observed in CD4+ T cells absolute numbers in
DF patients compared to healthy controls (p=0.01).
B. Kinetic changes of CD4/CD8 ratio in DHF vs DF patients
late phase. Only one Dengue Hemorrhagic Fever patients elevated slightly in first and
second time points (Figure 1). The decrease of CD4/CD8 ratio was not only found in
the Dengue Hemorrhagic Fever patients, but also in the Dengue Fever patients. The
eight of thirteen Dengue Fever patients declined the ratio of CD4/CD8 T cells
between early and late phase, whereas five Dengue Fever patients rised up gradually
at late phase.
C. The levels of chemokines (RANTES, MIP-1a, Mig) in DHF vs DF patients and
healthy donors
All the serum levels of three chemokines RANTES(DHF:13.69±3.46 ng/ml;
DF:19.56±2.74 ng/ml), and Mig(DHF:653.45±85.89 pg/ml; DF:664.63±59.60 pg/ml)
in dengue patients were significantly higher than healthy controls ( p<0.01)（Table 6;
Figure 2, 3）whereas the serum level of MIP-1α in dengue patients were significantly
（DHF:26.99±11.56 pg/ml; DF:38.59±9.86 pg/ml）lower than healthy controls(p<0.01)
（Table 6, Fig3）
D. Variation of the serum levels of chemokines at different days after onset of
fever in DHF vs DF patients.
The mean serum levels of Mig(DHF:763.83±118.43 pg/ml; DF:713.28±67.08
pg/ml) after fever onset ≤ 7 days were higher than those after fever onset＞7 days in
both DHF(IP10: 2.74±0.98 ng/ml; Mig:487.88±102.3 pg/ml) and DF(Mig:580.96±
113.86 pg/ml) patients.. However, the serum levels of RANTES after fever onset ≤ 7
days(DHF:9.78±3.25 ng/ml; DF:11.82±2.10 ng/ml) was lower than that after fever
onset＞7 days(DHF:19.57±6.94 ng/ml; DF:33.19±5.72 ng/ml). In addition, the levels
of RANTES, IP-10 and Mig at two different time periods after fever onset were
significantly higher than healthy controls（p<0.01） whereas the levels of MIP-1α at
two different time periods after fever onset were significantly lower than healthy
controls（p<0.01）.
Table 2. The demographic characteristics and medical history of study subjects in chemokine studies in Taiwan, 2003 Characteristics DHF (n=34) DF (n=90) Healthy Controls (n=14) Age, years(Mean±SD) 50.59±13.78 44.34±14.83 28.78±7.08 <30 2 (5.88%) 17 (18.89%) 12 (85.71%) 30~44 7 (20.59%) 18 (20%) 1 (7.14%) 45~59 17 (50%) 46 (51.11%) 1 (7.14%) 60~74 8 (23.53%) 9 (10%) 0 Gender Males 18 (51.52%) 49 (54.44%) 9 (64.29%) Females 16 (48.48%) 41 (45.56%) 5 (35.71%) Clinical History DM 10 (29.41%) 13 (14.44%) Asthma 2 (5.88%) 0 Gout 0 2 (2.22%) HBsAg(+) 0 3 (3.33%) DM+Gout 2 (5.88%) 0 DM+HbsAg(+) 0 3 (3.33%) Samples Collected at Days after the Onset of
Fever
≦7 days 20 (58.82%) 59 (65.56%)
Table 3. Comparison of T cell subsets among DHF versus DF patients adjusted the medical history and healthy controls in Taiwan, 2003 * P values are Wilcoxon rank sum comparisons of data from the columns of Healthy controls.
＃NS = not significant (p >0.05)
DHF(n=10) DF(n=63) Healthy Control (n=46)
CD Markers and Chemokine Receptors
Mean±SE P value* Mean±SE P value* Mean±SE
CD4 (% of CD3) 36.34±5.18 NS 33.19±2.21 0.03 40.13±2.35 CD62L+CD45RO- (%of CD4) 7.96±5.32 NS＃ 9.44±2.10 NS 18.24±3.56 CD62L+CD45RO+ (%of CD4) 8.17±5.31 NS 10.11±2.02 NS 11.19±2.20 CD62L-CD45RO+ (%of CD4) 9.88±6.03 NS 12.61±2.53 NS 9.28±2.02 CCR5 (%of CD4) 5.12±1.71 NS 7.02±1.16 NS 4.20±0.82 CXCR3 (%of CD4) 19.76±5.99 NS 21.81±2.69 NS 21.53±2.85 CD8 (% of CD3) 27.34±3.60 NS 30.20±1.89 NS 31.88±1.62 CD62L+CD45RO- (%of CD8) 7.09±4.49 NS 7.07±1.79 NS 19.44±4.07 CD62L+CD45RO+(%of CD8) 4.66±2.59 NS 6.15±1.62 NS 3.09±0.71 CD62L-CD45RO+ (%of CD8) 9.91±5.18 NS 12.86±2.65 NS 12.02±2.39 CCR5 (%of CD8) 12.48±3.52 NS 13.93±2.02 NS 10.62±1.64 CXCR3 (%of CD8) 26.78±8.37 NS 23.75±2.87 0.001 43.39±4.40 CCR5+/CD62L+CD45RO-CD3+ 0.72±0.46 NS 0.48±0.17 NS 0.24±0.16 CCR5+/CD62L+CD45RO+ CD3+ 0.23±0.16 NS 0.57±0.32 NS 0.69±0.42 CCR5+/CD62L-CD45RO+ CD3+ 2.66±2.01 NS 1.99±0.87 NS 1.79±0.98 CXCR3+/ CD62L+CD45RO-CD3+ 6.59±3.40 NS 7.37±2.10 NS 7.03±2.07 CXCR3+/ CD62L+CD45RO+CD3+ 10.45±6.97 NS 4.80±1.83 NS 6.14±2.42 CXCR3+/ CD62L-CD45RO+CD3+ 9.58±6.39 NS 5.84±2.08 NS 7.25±2.84
Table 6. Levels of Chemokine in the serum samples of DHF versus DF patients adjusted medical history
DHF DF Healthy controls Chemokines n Mean±SE P value＃ n Mean±SE P value# n Mean±SE
RANTES (ng/ml) 20 13.69±3.46 <0.01 69 19.56±2.74 <0.001 14 2.21±0.78 IP-10 (ng/ml) 20 4.74±0.69 a <0.001 56 3.39±0.63 <0.001 9 0.15±0.03 Mig (pg/ml) 20 653.45±85.89 <0.001 69 664.63±59.60 <0.001 13 190.85±22.53 MIP-1α (pg/ml) 20 26.99±11.56 <0.001 69 38.59±9.86 <0.001 14 92.47±13.55
# P value compared to Healthy controls a.P <0.05, vs. DF patients
DISCUSSION
This research focuses on the study of possible roles of chemokines and chemokine
receptors from innate immunity to adaptive immunity in dengue patients manifested
different clinical severity. Several major findings have not been documented in
literature.
A. Differences in Dengue Patients versus Healthy Controls: Kinetic Changes of
CD4/CD8 ratio in DHF and DF Patients
Dengue patients are usually leukopenic for several days during the acute
infection. Our observation that Dengue patients, regardless DHF or DF had lower
expression of CD4+ T and CD8+ T cells than healthy donors.
The ratio of CD4/CD8 T cells in DHF patients declined at late phase（After fever
onset ＞7days）.The 8 of 13 Dengue Fever patients declined the ratio of CD4/CD8 T
cells between early and late phase, too. The appearance of atypical lymphocytes may
be the T-cytotoxic/suppressor cells（CD3
+/CD8
+T cells）that contribute to the
imbalance between CD4 and CD8 T cells during dengue infection. The CD4/CD8
ratio changes was observed within two time points（≤ 7 days and ＞7 days after fever
onset）. Frequent analysis of the immune parameters after dengue infection will help
to understand the interaction between dengue virus and the host.
B. Chemokines
After dengue virus infection, various chemokines were released with different
quantities, durations and kinetics. The levels of RANTES, and Mig were higher than
healthy controls. By contrast, the levels of MIP-1α was lower compared to healthy
controls, whereas the levels of MIP-1α had different magnitude and kinetics of
secretion in Dengue Hemorrhagic Fever and Dengue Fever patients. Secretion of
MIP-1α may have roles in the immunopathology and may contribute to fever and
bone marrow suppression observed in Dengue Fever and Dengue Hemorrhagic Fever
patients【
Spain- Santana et al., 2001
】. Paradoxically, the fact that MIP-1α recruit
monocytes to the site of infection might provide dengue virus infection. Dendritic
calls are potent antigen-presenting cells that can initiate immune responses by
presenting antigens to secondary lymphoid and prime naïve T cells there. It is found
that the ability of dengue virus to infect both human dendritic cells and skin
Langerhans cell【
Libraty et al., 2001
】
.Maturing DC are also an abundant and strategic
source of chemokines. It’s temping to speculate that these lower levels of MIP-1α
may affect dengue virus infected DC undergo maturation and transport dengue virus
antigen to lymphoids organs to initiate immunity. Other factors, such initial burst
chemokines of DC response to acute viremia may also play a role and there warrant
further study at this issue.
In addition, secretion of RANTES persisted at high levels long after fever onset
in Dengue Hemorrhagic Fever and Dengue Fever patients. This might result from
stability of this mediators or constant production.
C. Immunopathological Significanc
In our present study, we attempted to obtain an integrated view of the
chemokine-chemokine receptors of human dengue virus infection by using Dengue
Hemorrhagic Fever and Dengue Fever patients’ repeat serum samples and comparing
the production kinetics and dose responses.
The clinical symptoms of Dengue Fever and Dengue Hemorrhagic Fever present
the signs of local inflammation, which may result from extravasation of lymphocytes
to sites of infection. The onset and peak of chemokine and chemokine receptor
production by different dengue virus infected target cells indicated that these
molecules may play a role in early recruitment of different subsets of leukocytes and
participate in the early response to viral infection as well as tissue injury【
Okayama et
al., 2000
】. These may suggest that a possible cooperative interaction between these
target cells and lymphocyte trafficking by different production of chemokines
We found the serum levels of RANTES, IP-10 and Mig were higher in Dengue
Hemorrhagic Fever and Dengue Fever patients. RANTES, IP-10, and Mig were
shown to recruit and activate T lymphocytes with memory phenocyte【
Raghupathy et
al., 1998
】and then might b important for rapid T cell effector functions during
secondary dengue virus infection.
It’s known that MIP-1a, RANTES, and IP-10 can induce NK cells activation,
chemotaxis, adhesion and transendothelial migration. Therefore, regulation of NK
cells activity by these mediators may affect dengue virus infection and tissue injury.
References
Adema GJ, Hartgers F, Verstraten R, de Vries E, Marland G, Menon S, Foster J, Xu Y, Nooyen P, McClanahan T, Bacon KB, Figdor CG. A dendritic-cell-derived C-C chemokine that preferentially attracts naive T cells. Nature. 1997; 387: 713-7.
Afford SC, Fisher NC, Neil DA, Fear J, Brun P, Hubscher SG, Adams DH. Distinct patterns of chemokine expression are associated with leukocyte recruitment in alcoholic hepatitis and alcoholic cirrhosis. J Pathol. 1998; 186: 82-9.
Alam R, Stafford S, Forsythe P, Harrison R, Faubion D, Lett-Brown MA, Grant JA. RANTES is a chemotactic and activating factor for human eosinophils. J Immunol. 1993; 150: 3442-8.
Anderson R, Wang S, Osiowy C, Issekutz AC. Activation of endothelial cells via antibody-enhanced dengue virus infection of peripheral blood monocytes. J Virol. 1997; 71: 4226-32.
Andrew DL. The role of chemokines in linking innate and adaptive immunity. Curr Opin Immunol. 2002; 14: 129-35.
Ansel KM, McHeyzer-Williams LJ, Ngo VN, McHeyzer-Williams MG, Cyster JG. In vivo-activated CD4 T cells upregulate CXC chemokine receptor 5 and reprogram their response to lymphoid chemokines. J Exp Med. 1999; 190: 1123-34.
Avirutnan P, Malasit P, Seliger B, Bhakdi S, Husmann M. Dengue virus infection of human endothelial cells leads to chemokine production, complement activation, and apoptosis. J Immunol. 1998; 161: 6338-46.
Baggiolini M, Dewald B, Moser B. Human chemokines: an update. Annu Rev Immunol. 1997; 15: 675-705.
Barnes WJ, Rosen L. Fatal hemorrhagic disease and shock associated with primary dengue infection on a Pacific island. Am J Trop Med Hyg. 1974; 23: 495-506.
Bazan JF, Bacon KB, Hardiman G, Wamg W, Soo K, Rossi D, Greaves DR, Zlotnik A, Schall TJ. A new class of membrane bound chemokine with a CX3C motif. Nature. 1997; 385: 640-4.
Benito JM, Zabay JM, Gil J, Bermejo M, Escudero A, Sanchez E, Fernandez-Cruz E. Quantitative alterations of the functionally distinct subsets of CD4 and CD8 T lymphocytes in asymptomatic HIV
infection: changes in the expression of CD45RO, CD45RA, CD11b, CD38, HLA-DR, and CD25 antigens.J Acquir Immune Defic Syndr Hum Retrovirol. 1997; 14: 128-35.
Bethell DB, Flobbe K, Cao XT, Day NP, Pham TP, Buurman WA, Cardosa MJ, White NJ, Kwiatkowski D. Pathophysiologic and prognostic role of cytokines in dengue hemorrhagic fever. J Infect Dis. 1998 ;177: 778-82.
Bhamarapravati N., Dengue and Dengue Hemorrhagic Fever, in: Gubler D.J., Kuno G.（Eds.）, CAB Internation al, New York, 1997, pp. 115-132.
Bischoff SC, Krieger M, Brunner T, Rot A, von Tscharner V, Baggiolini M, Dahinden CA. RANTES and related chemokines activate human basophil granulocytes through different G protein-coupled receptors. Eur J Immunol. 1993; 23: 761-7.
Blanco J, Cabrera C, Jou A, Ruiz L, Clotet B, Este JA. Chemokine and chemokine receptor expression after combined anti-HIV-1 interleukin-2 therapy. AIDS. 1999; 13: 547-55.
Blom T, Huang R, Aveskogh M, Nilsson K, Hellman L. Phenotypic characterization of KU812, a cell line identified as an immature human basophilic leukocyte. Eur J Immunol. 1992; 22: 2025-32.
Bonecchi R, Bianchi G, Bordignon PP, D'Ambrosio D, Lang R, Borsatti A, Sozzani S, Allavena P, Gray PA, Mantovani A, Sinigaglia F. Differential expression of chemokine receptors and chemotactic responsiveness of type 1 T helper cells (Th1s) and Th2s. J Exp Med. 1998; 187: 129-34.
Bone-Larson CL, Simpson KJ, Colletti LM, Lukacs NW, Chen SC, Lira S, Kunkel SL, Hogaboam CM. The role of chemokines in the immunopathology of the liver. Immunol Rev. 2000; 177: 8-20.
Bonnet D, Lemoine FM, Najman A, Guigon M. Comparison of the inhibitory effect of AcSDKP, TNF-alpha, TGF-beta, and MIP-1 alpha on marrow-purified CD34+ progenitors. Exp Hematol. 1995; 23: 551-6.
Brandt WE, McCown JM, Top FH Jr, Bancroft WH, Russell PK. Effect of passage history on dengue-2 virus replication in subpopulations of human leukocytes.
Infect Immun. 1979; 26: 534-41.
Breitfeld D, Ohl L, Kremmer E, Ellwart J, Sallusto F, Lipp M, Forster R. Follicular B helper T cells express CXC chemokine receptor 5, localize to B cell follicles, and support immunoglobulin production. J Exp Med. 2000; 192: 1545-52.
Broxmeyer HE, Sherry B, Cooper S, Lu L, Maze R, Beckmann MP, Cerami A, Ralph P. Comparative analysis of the human macrophage inflammatory protein family of cytokines (chemokines) on proliferation of human myeloid progenitor cells. Interacting effects involving suppression, synergistic suppression, and blocking of suppression. J Immunol. 1993; 150: 3448-58.
Burke DS, Nisalak A, Johnson DE, Scott RM. A prospective study of dengue infections in Bangkok. Am J Trop Med Hyg. 1988; 38: 172-80.
Butcher EC, Williams M, Youngman K, Rott L, Briskin M. Lymphocyte trafficking and regional immunity. Adv Immunol 1999;72:209-253.
Butterfield JH, Weiler D, Dewald G, Gleich GJ. Establishment of an immature mast cell line from a patient with mast cell leukemia. Leuk Res. 1988; 12: 345-55.
Campbell JJ, Hedrick J, Zlotnik A, Siani MA, Thompson DA, Butcher EC. Chemokines and the arrest of lymphocytes rolling under flow conditions. Science. 1998; 279: 381-4.
Cella M, Salio M, Sakakibara Y, Langen H, Julkunen I, Lanzavecchia A. Maturation, activation, and protection of dendritic cells induced by double-stranded RNA. J Exp Med. 1999; 189: 821-9.
Chantry D, Romagnani P, Raport CJ, Wood CL, Epp A, Romagnani S, Gray PW. Macrophage-derived chemokine is localized to thymic medullary epithelial cells and is a chemoattractant for CD3(+), CD4(+), CD8(low) thymocytes. Blood. 1999; 94: 1890-8.
Chen Y, Maguire T, Hileman RE, Fromm JR, Esko JD, Linhardt RJ, Marks RM. Dengue virus infectivity depends on envelope protein binding to target cell heparan sulfate. Nat Med. 1997; 3: 866-71.
Chen YC, Wang SY. Activation of terminally differentiated human monocytes/macrophages by dengue virus: productive infection, hierarchical production of innate cytokines and chemokines. J Virol. 2002; 76: 9877-87.
Cocchi F, DeVico AL, Garzino-Demo A, Arya SK, Gallo RC, Lusso P. Identification of RANTES, MIP-1 alpha, and MIP-1 beta as the major HIV-suppressive factors produced by CD8+ T cells. Science. 1995; 270: 1811-5.
Cohen J. AIDS research. Receptor mutations help slow disease progression. Science. 1996; 273: 1797-8.
Cole KE, Strick CA, Paradis TJ, Ogborne KT, Loetscher M, Gladue RP, Lin W, Boyd JG, Moser B, Wood DE, Sahagan BG, Neote K. Interferon-inducible T cell alpha chemoattractant (I-TAC): a novel non-ELR CXC chemokine with potent activity on activated T cells through selective high affinity binding to CXCR3. J Exp Med. 1998; 187: 2009-21.
Colletti LM, Kunkel SL, Walz A, Burdick MD, Kunkel RG, Wilke CA, Strieter RM. The role of cytokine networks in the local liver injury following hepatic ischemia/reperfusion in the rat. Hepatology. 1996; 23: 506-14.
Cook DN, Prosser DM, Forster R, Zhang J, Kuklin NA, Abbondanzo SJ, Niu XD, Chen SC, Manfra DJ, Wiekowski MT, Sullivan LM, Smith SR, Greenberg HB, Narula SK, Lipp M, Lira SA. CCR6 mediates dendritic cell localization, lymphocyte homeostasis, and immune responses in mucosal tissue. Immunity. 2000; 12: 495-503.
Cyster JG, Ansel KM, Reif K, Ekland EH, Hyman PL, Tang HL, Luther SA, Ngo VN. Follicular stromal cells and lymphocyte homing to follicles. Immunol Rev. 2000; 176: 181-93.
Cyster JG. Chemokines and cell migration in secondary lymphoid organs. Science. 1999; 286: 2098-102.
Czaja MJ, Geerts A, Xu J, Schmiedeberg P, Ju Y.Monocyte chemoattractant protein 1 (MCP-1) expression occurs in toxic rat liver injury and human liver disease.
J Leukoc Biol. 1994; 55: 120-6.
Dean M, Carrington M, Winkler C, Huttley GA, Smith MW, Allikmets R. Hemophilia growth and development study, Multicenter AIDS cohort study, Multicenter Hemophilia Cohort Study, San Francisco City Cohort, ALIVE study, and S.J.O’Brien, S.J., Genetic Restriction of HIV-1 Infection and Progression to AIDS by a deletion allele of the CCR5 structural gene. Science 1996;273:1856-62. Dieu MC, Vanbervliet B, Vicari A, Bridon JM, Oldham E, Ait-Yahia S, Briere F, Zlotnik A, Lebecque S, Caux C. Selective recruitment of immature and mature dendritic cells by distinct chemokines expressed in different anatomic sites.
J Exp Med. 1998; 188: 373-86.
D’Souza MP, Harden VA. Chemokines and HIV-1 second receptors-confluence of two fields generates optimism in AIDS research. Nature Med 1996; 2:1293-300.
Edgington SM. Chemokines in cardiovascular disease. Do chemoattractant cytokines regulate the progression of atherosclerosis? Biotechnology (N Y). 1993; 11: 676-8, 681.
Farber JM. A macrophage mRNA selectively induced by gamma-interferon encodes a member of the platelet factor 4 family of cytokines. Proc Natl Acad Sci U S A. 1990; 87: 5238-42.
Fisher-Hoch SP, Mitchell SW, Sasso DR, Lange JV, Ramsey R, McCormick JB. Physiological and immunologic disturbances associated with shock in a primate model of Lassa fever. J Infect Dis. 1987; 155: 465-74.
Forster R, Emrich T, Kremmer E, Lipp M. Expression of the G-protein--coupled receptor BLR1 defines mature, recirculating B cells and a subset of T-helper memory cells. Blood. 1994; 84: 830-40.
Forster R, Mattis AE, Kremmer E, Wolf E, Brem G, Lipp M. A putative chemokine receptor, BLR1, directs B cell migration to defined lymphoid organs and specific anatomic compartments of the spleen. Cell. 1996; 87: 1037-47.
Forster R, Schubel A, Breitfeld D, Kremmer E, Renner-Muller I, Wolf E, Lipp M. CCR7 coordinates the primary immune response by establishing functional microenvironments in secondary lymphoid organs. Cell. 1999; 99: 23-33.
Fritz RS, Hayden FG, Calfee DP, Cass LM, Peng AW, Alvord WG, Strober W, Straus SE. Nasal cytokine and chemokine responses in experimental influenza A virus infection: results of a placebo-controlled trial of intravenous zanamivir treatment.
J Infect Dis. 1999; 180: 586-93.
Gasperini S, Marchi M, Calzetti F, Laudanna C, Vicentini L, Olsen H, Murphy M, Liao F, Farber J, Cassatella MA. Gene expression and production of the monokine induced by IFN-gamma (MIG), IFN-inducible T cell alpha chemoattractant (I-TAC), and IFN-gamma-inducible protein-10 (IP-10) chemokines by human neutrophils. J Immunol. 1999; 162: 4928-37.
Giovannetti A, Ensoli F, Mazzetta F, De Cristofaro M, Pierdominici M, Muratori DS, Fiorelli V, Aiuti F.CCR5 and CXCR4 chemokine receptor expression and beta-chemokine production during early T cell repopulation induced by highly active anti-retroviral therapy. Clin Exp Immunol. 1999; 118: 87-94. Godiska R, Chantry D, Raport CJ, Sozzani S, Allavena P, Leviten D, Mantovani A, Gray PW. Human macrophage-derived chemokine (MDC), a novel chemoattractant for monocytes, monocyte-derived dendritic cells, and natural killer cells. J Exp Med. 1997;185: 1595-604.
Graham GJ, Zhou L, Weatherbee JA, Tsang ML, Napolitano M, Leonard WJ, Pragnell IB. Characterization of a receptor for macrophage inflammatory protein 1 alpha and related proteins on human and murine cells. Cell Growth Differ. 1993; 4: 137-46.
Green S, Vaughn DW, Kalayanarooj S, Nimmannitya S, Suntayakorn S, Nisalak A, Rothman AL, Ennis FA. Elevated plasma interleukin-10 levels in acute dengue correlate with disease severity.J Med Virol. 1999; 59: 329-34.
Gunn MD, Kyuwa S, Tam C, Kakiuchi T, Matsuzawa A, Williams LT, Nakano H. Mice lacking expression of secondary lymphoid organ chemokine have defects in lymphocyte homing and dendritic cell localization. J Exp Med. 1999; 189: 451-60.
Guzman MG, Kouri GP, Bravo J, Soler M, Vazquez S, Morier L. Dengue hemorrhagic fever in Cuba, 1981: a retrospective seroepidemiologic study. Am J Trop Med Hyg. 1990;42: 179-84.
Halstead S.B., Dengue and Dengue Hemorrhagic Fever, in: Gubler D.J., Kuno G.（Eds.）, CAB Internation al, New York, 1997, pp. 23-44.
Halstead SB. Antibody, macrophages, dengue virus infection, shock, and hemorrhage: a pathogenetic cascade. Rev Infect Dis. 1989; 11 Suppl 4:S830-9.
Hedrick JA, Zlotnik A. Lymphotactin. Clin Immunol Immunopathol. 1998; 87: 218-22.
Hober D, Poli L, Roblin B, Gestas P, Chungue E, Granic G, Imbert P, Pecarere JL, Vergez-Pascal R, Wattre P, et al. Serum levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and interleukin-1 beta (IL-1 beta) in dengue-infected patients. Am J Trop Med Hyg. 1993; 48: 324-31. Horn F, Weare J, Beukers MW, Horsch S, Bairoch A, Chen W. GPCRDB: an information system for G protein-coupled receptors. Nucleic Acids Res. 1998; 26: 275-9.
Horuk R, Chitnis CE, Darbonne WC, Colby TJ, Rybicki A, Hadley TJ. A receptor for the malarial parasite Plasmodium vivax: The erythrocyte chemokine receptor. Science 1993; 261: 1182-4.
Huang YH, Liu CC, Wang ST, Lei HY, Liu HL, Lin YS, Wu HL, Yeh TM. Activation of coagulation and fibrinolysis during dengue virus infection. J Med Virol. 2001; 63: 247-51.
Johnson U, Ohlsson K, Olsson I. Effects of granulocyte neutral proteases on complement components. Scand J Immunol. 1976; 5: 421-6.
Juffrie M, van Der Meer GM, Hack CE, Haasnoot K, Sutaryo, Veerman AJ, Thijs LG. Inflammatory mediators in dengue virus infection in children: interleukin-8 and its relationship to neutrophil degranulation. Infect Immun. 2000; 68: 702-7.
Kalayanarooj S, Vaughn DW, Nimmannitya S, Green S, Suntayakorn S, Kunentrasai N, Viramitrachai W, Ratanachu-eke S, Kiatpolpoj S, Innis BL, Rothman AL, Nisalak A, Ennis FA. Early clinical and laboratory indicators of acute dengue illness. J Infect Dis. 1997; 176: 313-21.
Kameyoshi Y, Dorschner A, Mallet AI, Christophers E, Schroder JM. Cytokine RANTES released by thrombin-stimulated platelets is a potent attractant for human eosinophils. J Exp Med. 1992; 176: 587-92.
Kasama T, Strieter RM, Lukacs NW, Burdick MD, Kunkel SL. Regulation of neutrophil-derived chemokine expression by IL-10. J Immunol. 1994; 152: 3559-69.
Keane MP, Arenberg DA, Moore BB, Addison CL, Strieter RM. CXC chemokines and angiogenesis/angiostasis. Proc Assoc Am Physicians. 1998; 110: 288-96.
Kelner GS, Zlotnik A. Cytokine production profile of early thymocytes and the characterization of a new class of chemokine. J Leukoc Biol. 1995; 57: 778-81.
Kim CH, Pelus LM, White JR, Applebaum E, Johanson K, Broxmeyer HE. CK beta-11/macrophage inflammatory protein-3 beta /EB11-ligand chemokine is an efficacious chemoattractant for T and B cells. J Immunol.1998; 160: 2418-24.
Kim CH, Rott LS, Clark-Lewis I, Campbell DJ, Wu L, Butcher EC. Subspecialization of CXCR5+ T cells: B helper activity is focused in a germinal center-localized subset of CXCR5+ T cells. J Exp Med. 2001; 193: 1373-81.
King CA, Anderson R, Marshall JS. Dengue virus selectively induces human mast cell chemokine production. J Virol. 2002;76:8408-8419.
Kliks SC, Nisalak A, Brandt WE, Wahl L, Burke DS. Antibody-dependent enhancement of dengue virus growth in human monocytes as a risk factor for dengue hemorrhagic fever. Am J Trop Med Hyg. 1989; 40: 444-51.
Koch AE, Kunkel SL, Harlow LA, Mazarakis DD, Haines GK, Burdick MD, Pope RM, Strieter RM. Macrophage inflammatory protein-1 alpha. A novel chemotactic cytokine for macrophages in
rheumatoid arthritis. J Clin Invest. 1994; 93: 921-8.
Koniaris LG, Zimmers-Koniaris T, Hsiao EC, Chavin K, Sitzmann JV, Farber JM. Cytokine-responsive gene-2/IFN-inducible protein-10 expression in multiple models of liver and bile duct injury suggests a role in tissue regeneration. J Immunol. 2001; 167: 399-406.
Kurane I., Ennis F.A. Dengue and Dengue Hemorrhagic Fever, in: Gubler D.J., Kuno G.（Eds.）, CAB Internation al, New York, 1997, pp. 273-290.
Leitmeyer KC, Vaughn DW, Watts DM, Salas R, Villalobos I, de Chacon, Ramos C, Rico-Hesse R. Dengue virus structural differences that correlate with pathogenesis.
J Virol. 1999; 73: 4738-47.
Lenardo M, Chan KM, Hornung F, McFarland H, Siegel R, Wang J, Zheng L. Mature T lymphocyte apoptosis--immune regulation in a dynamic and unpredictable antigenic environment. Annu Rev Immunol. 1999; 17: 221-53.
Lentsch AB, Yoshidome H, Cheadle WG, Miller FN, Edwards MJ. Chemokine involvement in hepatic ischemia/reperfusion injury in mice: roles for macrophage inflammatory protein-2 and KC. Hepatology. 1998; 27: 1172-7.
Libraty DH, Pichyangkul S, Ajariyakhajorn C, Endy TP, Ennis FA. Human dendritic cells are activated by dengue virus infection: enhancement by gamma interferon and implications for disease pathogenesis.
J Virol. 2001; 75: 3501-8.
Lin YL, Liu CC, Chuang JI, Lei HY, Yeh TM, Lin YS, Huang YH, Liu HS. Involvement of oxidative stress, NF-IL-6, and RANTES expression in dengue-2-virus-infected human liver cells. Virology. 2000; 276: 114-26.
Liu CC, Huang KJ, Lin YS, Yeh TM, Liu HS, Lei HY. Transient CD4/CD8 ratio inversion and aberrant immune activation during dengue virus infection. J Med Virol. 2002;68:241-252.
Loetscher P, Uguccioni M, Bordoli L, Baggiolini M, Moser B, Chizzolini C, Dayer JM. CCR5 is characteristic of Th1 lymphocytes. Nature. 1998; 391: 344-5.
Luster AD. Chemokines-chemotactic cytokines that mediate inflammation. N Engl J Med. 1998; 338: 436-45.
and interferon inducible protein-10 in serum are associated with fatal infections in acute lassa fever. J infect Dis. 2001;183:1713-21
Marra F, DeFranco R, Grappone C, Milani S, Pastacaldi S, Pinzani M, Romanelli RG, Laffi G, Gentilini P. Increased expression of monocyte chemotactic protein-1 during active hepatic fibrogenesis: correlation with monocyte infiltration.
Am J Pathol. 1998; 152: 423-30.
Marra F, Romanelli RG, Giannini C, Failli P, Pastacaldi S, Arrighi MC, Pinzani M, Laffi G, Montalto P, Gentilini P. Monocyte chemotactic protein-1 as a chemoattractant for human hepatic stellate cells. Hepatology. 1999; 29: 140-8.
Michelmann I, Bockmann D, Nurnberger W, Eckhof-Donovan S, Burdach S, Gobel U. Thrombocytopenia and complement activation under recombinant TNF alpha/IFN gamma therapy in man. Ann Hematol. 1997; 74: 179-84.
Miller MD, Krangel MS. Biology and biochemistry of the chemokines: a family of chemotactic and inflammatory cytokines. Crit Rev Immunol. 1992; 12: 17-46.
Moller A, Lippert U, Lessmann D, Kolde G, Hamann K, Welker P, Schadendorf D, Rosenbach T, Luger T, Czarnetzki BM. Human mast cells produce IL-8. J Immunol. 1993; 151: 3261-6.
Morelli A, Larregina A, Chuluyan I, Kolkowski E, Fainboim L. Expression and modulation of C5a receptor (CD88) on skin dendritic cells. Chemotactic effect of C5a on skin migratory dendritic cells. Immunology. 1996; 89: 126-34.
Morens DM. Antibody-dependent enhancement of infection and the pathogenesis of viral disease. Clin Infect Dis. 1994; 19: 500-12.
Morland CM, Fear J, McNab G, Joplin R, Adams DH. Promotion of leukocyte transendothelial cell migration by chemokines derived from human biliary epithelial cells in vitro. Proc Assoc Am Physicians. 1997; 109: 372-82.
Moser B, Loetscher P. Lymphocyte traffic control by chemokines. Nature Immunol. 2001;2:123-128. Mosmann TR, Coffman RL. TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Annu Rev Immunol. 1989; 7: 145-73.
Mukaida N, Harada A, Matsushima K. Interleukin-8 (IL-8) and monocyte chemotactic and activating factor (MCAF/MCP-1), chemokines essentially involved in inflammatory and immune reactions. Cytokine Growth Factor Rev. 1998; 9: 9-23.
Murai M, Yoneyama H, Harada A, Yi Z, Vestergaard C, Guo B, Suzuki K, Asakura H, Matsushima K. Active participation of CCR5(+)CD8(+) T lymphocytes in the pathogenesis of liver injury in graft-versus-host disease. J Clin Invest. 1999; 104: 49-57.
Murgue B, Cassar O, Deparis X, Guigon M, Chungue E. Implication of macrophage inflammatory protein-1alpha in the inhibition of human haematopoietic progenitor growth by dengue virus. J Gen Virol. 1998; 79: 1889-93.
Nagasawa T. A chemokine, SDF-1/PBSF, and its receptor, CXC chemokine receptor 4, as mediators of hematopoiesis. Int J Hematol. 2000; 72: 408-11.
Narumi S, Yoneyama H, Inadera H, Nishioji K, Itoh Y, Okanoue T, Matsushima K. TNF-alpha is a potent inducer for IFN-inducible protein-10 in hepatocytes and unaffected by GM-CSF in vivo, in contrast to IL-1beta and IFN-gamma. Cytokine. 2000; 12: 1007-16.
Neote K, Digregorio D, Mark JY, Horuk R, Schall TJ. Molecular cloning, functional expression, and signaling characteristics of C-C chemokine receptor. Cell. 1993; 72: 415-25.
Neville LF, Mathiak G, Bagasra O. The immunobiology of interferon-gamma inducible protein 10 kD (IP-10): a novel, pleiotropic member of the C-X-C chemokine superfamily. Cytokine Growth Factor Rev. 1997; 8: 207-19.
Ngo VN, Tang HL, Cyster JG. Epstein-Barr virus-induced molecule 1 ligand chemokine is expressed by dendritic cells in lymphoid tissues and strongly attracts naive T cells and activated B cells. J Exp Med. 1998; 188: 181-91.
Nibbs RJ, Wylie SM, Yang J, Landau NR, Graham GJ. Cloning and characterization of a novel promiscuous human beta-chemokine receptor D6. J Biol Chem. 1997; 272: 32078-83.
Nishioji K, Okanoue T, Itoh Y, Narumi S, Sakamoto M, Nakamura H, Morita A, Kashima K. Increase of chemokine interferon-inducible protein-10 (IP-10) in the serum of patients with autoimmune liver diseases and increase of its mRNA expression in hepatocytes. Clin Exp Immunol. 2001; 123: 271-9. Noah TL, Becker S. Chemokines in nasal secretions of normal adults experimentally infected with
respiratory syncytial virus. Clin Immunol. 2000; 97: 43-9.
Okayama Y, Kirshenbaum AS, Metcalfe DD. Expression of a functional high-affinity IgG receptor, Fc gamma RI, on human mast cells: Up-regulation by IFN-gamma. J Immunol. 2000;164: 4332-9.
Ostrowski MA, Justement SJ, Catanzaro A, Hallahan CA, Ehler LA, Mizell SB, Kumar PN, Mican JA, Chun TW, Fauci AS. Expression of chemokine receptors CXCR4 and CCR5 in HIV-1-infected and uninfected individuals. J Immunol. 1998; 161: 3195-201.
Park JW, Gruys ME, McCormick K, Lee JK, Subleski J, Wigginton JM, Fenton RG, Wang JM, Wiltrout RH. Primary hepatocytes from mice treated with IL-2/IL-12 produce T cell chemoattractant activity that is dependent on monokine induced by IFN-gamma (Mig) and chemokine responsive to gamma-2 (Crg-2).J Immunol. 2001; 166: 3763-70.
Psenak O. Stromal cell-derived factor 1 (SDF-1). Its structure and function. Cas Lek Cesk. 2001; 140: 355-63.
Qin S, Rottman JB, Myers P, Kassam N, Weinblatt M, Loetscher M, Koch AE, Moser B, Mackay CR. The chemokine receptors CXCR3 and CCR5 mark subsets of T cells associated with certain inflammatory reactions. J Clin Invest. 1998; 101: 746-54.
Quillent C, Oberlin E, Braun J, Rousset D, Gonzalez-Canali G, Metais P, Montagnier L, Virelizier JL, Arenzana-Seisdedos F, Beretta A. HIV-1-resistance phenotype conferred by combination of two separate inherited mutations of CCR5 gene. Lancet. 1998; 351: 14-8.
Rabin RL, Roederer M, Maldonado Y, Petru A, Herzenberg LA, Herzenberg LA.Altered representation of naive and memory CD8 T cell subsets in HIV-infected children. J Clin Invest. 1995; 95: 2054-60. Raghupathy R, Chaturvedi UC, Al-Sayer H, Elbishbishi EA, Agarwal R, Nagar R, Kapoor S, Misra A, Mathur A, Nusrat H, Azizieh F, Khan MA, Mustafa AS. Elevated levels of IL-8 in dengue hemorrhagic fever. J Med Virol. 1998; 56: 280-5.
Rampart M, Van Damme J, Zonnekeyn L, Herman AG. Granulocyte chemotactic protein/interleukin-8 induces plasma leakage and neutrophil accumulation in rabbit skin. Am J Pathol. 1989; 135: 21-5. Rathanaswami P, Hachicha M, Sadick M, Schall TJ, McColl SR. Expression of the cytokine RANTES in human rheumatoid synovial fibroblasts. Differential regulation of RANTES and interleukin-8 genes by inflammatory cytokines. J Biol Chem. 1993; 268: 5834-9.
Rescigno M, Citterio S, Thery C, Rittig M, Medaglini D, Pozzi G, Amigorena S, Ricciardi-Castagnoli P. Bacteria-induced neo-biosynthesis, stabilization, and surface expression of functional class I molecules in mouse dendritic cells. Proc Natl Acad Sci U S A. 1998; 95: 5229-34.
Rico-Hesse R, Harrison LM, Salas RA, Tovar D, Nisalak A, Ramos C, Boshell J, de Mesa MT, Nogueira RM, da Rosa AT. Origins of dengue type 2 viruses associated with increased pathogenicity in the Americas. Virology. 1997; 230: 244-51.
Roederer M, Dubs JG, Anderson MT, Raju PA, Herzenberg LA, Herzenberg LA. CD8 naive T cell counts decrease progressively in HIV-infected adults. J Clin Invest. 1995; 95: 2061-6.
Romagnani S. Lymphokine production by human T cells in disease states. Annu Rev Immunol. 1994; 12: 227-57.
Rossi D and Zlotnik A. The biology of chemokines and their receptors. Annu Rev Immunol. 2000; 18: 217-42.
Rot A, Krieger M, Brunner T, Bischoff SC, Schall TJ, Dahinden CA. RANTES and macrophage inflammatory protein 1 alpha induce the migration and activation of normal human eosinophil granulocytes. J Exp Med. 1992; 176: 1489-95.
Rothman AL, Ennis FA. Immunopathogenesis of Dengue hemorrhagic fever. Virology. 1999; 257: 1-6. Sallusto F, Cella M, Danieli C, Lanzavecchia A. Dendritic cells use macropinocytosis and the mannose receptor to concentrate macromolecules in the major histocompatibility complex class II compartment: downregulation by cytokines and bacterial products. J Exp Med. 1995; 182: 389-400.
Sallusto F, Lanzavecchia A. Understanding dendritic cell and T-lymphocyte traffic through the analysis of chemokine receptor expression. Immunol Rev. 2000; 177: 134-40.
Sallusto F, Lenig D, Forster R, Lipp M, Lanzavecchia A. Two subsets of memory T lymphocytes with distinct homing potentials and effector functions. Nature. 1999; 401: 708-12.
Sallusto F, Palermo B, Lenig D, Miettinen M, Matikainen S, Julkunen I, Forster R, Burgstahler R, Lipp M, Lanzavecchia A. Distinct patterns and kinetics of chemokine production regulate dendritic cell function. Eur J Immunol. 1999; 29: 1617-25.
and coordinated switch in chemokine receptor expression during dendritic cell maturation. Eur J Immunol. 1998; 28: 2760-9.
Samson M, Edinger AL, Stordeur P, Rucker J, Verhasselt V, Sharron M, Govaerts C, Mollereau C, Vassart G, Doms RW, Parmentier M. ChemR23, a putative chemoattractant receptor, is expressed in monocyte-derived dendritic cells and macrophages and is a coreceptor for SIV and some primary HIV-1 strains.
Eur J Immunol. 1998; 28: 1689-700.
Samson M, Labbe O, Mollereau C, Vassart G, Parmentier M. Molecular cloning and functional expression of a new human CC-chemokine receptor gene. Biochemistry 1996; 35:3362-7.
Samson M, Libert F, Doranz BJ, Rucker J, Liesnard C, Farber CM, Saragosti S, Lapoumeroulie C, Cognaux J, Forceille C, Muyldermans G, Verhofstede C, Burtonboy G, Georges M, Imai T, Rana S, Yi Y, Smyth RJ, Collman RG, Doms RW, Vassart G, Parmentier M. Resistance to HIV-1 infection in caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene. Nature. 1996; 382: 722-5.
Sarris AH, Broxmeyer HE, Wirthmueller U, Karasavvas N, Cooper S, Lu L, Krueger J, Ravetch JV. Human interferon-inducible protein 10: expression and purification of recombinant protein demonstrate inhibition of early human hematopoietic progenitors. J Exp Med. 1993; 178: 1127-32.
Schaerli P, Willimann K, Lang AB, Lipp M, Loetscher P, Moser B. CXC chemokine receptor 5 expression defines follicular homing T cells with B cell helper function. J Exp Med. 2000; 192: 1553-62.
Schall TJ, Bacon K, Toy KJ, Goeddel DV. Selective attraction of monocytes and T lymphocytes of the memory phenotype by cytokine RANTES. Nature. 1990; 347: 669-71.
Schall TJ, Bacon KB. Chemokines, leukocyte trafficking, and inflammation. Curr Opin Immunol. 1994; 6: 865-73.
Schall TJ, Jongstra J, Dyer BJ, Jorgensen J, Clayberger C, Davis MM, Krensky AM. A human T cell-specific molecule is a member of a new gene family. J Immunol. 1988; 141: 1018-25.
Schmidt W, Egbring R, Havemann K. Effect of elastase-like and chymotrypsin-like neutral proteases from human granulocytes on isolated clotting factors. Thromb Res. 1975; 6: 315-29.
Schroder JM, Mrowietz U, Morita E, Christophers E. Purification and partial biochemical characterization of a human monocyte-derived, neutrophil-activating peptide that lacks interleukin 1 activity. J Immunol. 1987; 139: 3474-83.
Scott RM, Nimmannitya S, Bancroft WH, Mansuwan P. Shock syndrome in primary dengue infections. Am J Trop Med Hyg. 1976; 25: 866-74.
Seder RA, Paul WE. Acquisition of lymphokine-producing phenotype by CD4+ T cells. Annu Rev Immunol. 1994; 12: 635-73.
Shimizu Y, Murata H, Kashii Y. CC-chemokine receptor 6 and its ligand macrophage migration inhibitory protein 3 alpha might be involved in the amplification of focal necroinflammatory response in the liver. Hepatology. 2001; 34: 311-319.
Smedly LA, Tonnesen MG, Sandhaus RA, Haslett C, Guthrie LA, Johnston RB Jr, Henson PM, Worthen GS. Neutrophil-mediated injury to endothelial cells. Enhancement by endotoxin and essential role of neutrophil elastase. J Clin Invest. 1986; 77: 1233-43.
Sosman JA, Verma A, Moss S, Sorokin P, Blend M, Bradlow B, Chachlani N, Cutler D, Sabo R, Nelson M, Bruno E, Gustin D, Viana M, Hoffman R. Interleukin 10-induced thrombocytopenia in normal healthy adult volunteers: evidence for decreased platelet production. Br J Haematol. 2000; 111: 104-11. Sozzani S, Allavena P, D'Amico G, Luini W, Bianchi G, Kataura M, Imai T, Yoshie O, Bonecchi R, Mantovani A. Differential regulation of chemokine receptors during dendritic cell maturation: a model for their trafficking properties. J Immunol. 1998. 161: 1083-6.
Sozzani S, Sallusto F, Luini W, Zhou D, Piemonti L, Allavena P, Van Damme J, Valitutti S, Lanzavecchia A, Mantovani A. Migration of dendritic cells in response to formyl peptides, C5a, and a distinct set of chemokines. J Immunol. 1995; 155: 3292-5.
Spain-Santana TA, Marglin S, Ennis FA, Rothman AL. MIP-1 alpha and MIP-1 beta induction by dengue virus. J Med Virol. 2001; 65: 324-30.
Srichaikul T, Nimmannitya S. Haematology in dengue and dengue haemorrhagic fever. Baillieres Best Pract Res Clin Haematol. 2000 ; 13: 261-76.
Swain MG, Tjandra K, Kanwar S, Kubes P. Neutrophil adhesion is impaired in rat model of cholestasis. Gastroenterology. 1995; 109: 923-32.
Taub DD, Oppenheim JJ. Review of the chemokine meeting the Third International Symposium of Chemotactic Cytokines. Cytokine. 1993; 5: 175-9.
Taub DD, Sayers TJ, Carter CR, Ortaldo JR. Alpha and beta chemokines induce NK cell migration and enhance NK-mediated cytolysis. J Immunol. 1995; 155: 3877-88.
Tjandra K, Kubes P, Rioux K, Swain MG. Endogenous glucocorticoids inhibit neutrophil recruitment to inflammatory sites in cholestatic rats. Am J Physiol. 1996; 270: G821-5.
Tjandra K, Sharkey KA, Swain MG. Progressive development of a Th1-type hepatic cytokine profile in rats with experimental cholangitis. Hepatology. 2000; 31: 280-90.
Tsukamoto H, Lu SC. Current concepts in the pathogenesis of alcoholic liver injury. FASEB J. 2001; 15: 1335-49.
Tsuneyama K, Harada K, Yasoshima M, Hiramatsu K, Mackay CR, Mackay IR, Gershwin ME, Nakanuma Y. Monocyte chemotactic protein-1, -2, and -3 are distinctively expressed in portal tracts and granulomata in primary biliary cirrhosis: implications for pathogenesis. J Pathol. 2001; 193: 102-9. van Gorp EC, Minnema MC, Suharti C, Mairuhu AT, Brandjes DP, ten Cate H, Hack CE, Meijers JC. Activation of coagulation factor XI, without detectable contact activation in dengue haemorrhagic fever. Br J Haematol. 2001; 113: 94-9.
Varani J, Ginsburg I, Schuger L, Gibbs DF, Bromberg J, Johnson KJ, Ryan US, Ward PA. Endothelial cell killing by neutrophils. Synergistic interaction of oxygen products and proteases. Am J Pathol. 1989; 135: 435-8.
Vaughn DW, Green S, Kalayanarooj S, Innis BL, Nimmannitya S, Suntayakorn S, Endy TP, Raengsakulrach B, Rothman AL, Ennis FA, Nisalak A. Dengue viremia titer, antibody response pattern, and virus serotype correlate with disease severity. J Infect Dis. 2000; 181: 2-9.
von Andrian UH, Mackay CR. T-cell function and migration. Two sides of the same coin. N Engl J Med. 2000; 343: 1020-34.
Walz A, Schmutz P, Mueller C, Schnyder-Candrian S. Regulation and fuction of the CXC chemokine ENA-78 in monocytes and its role in disease. J Leukoc Biol. 1997; 62: 604-11.
chemokines JE, KC, and IP-10 gene in primary cultured murine hepatocytes. J Cell Physiol. 1999; 181: 361-70.
Warnock RA, Campbell JJ, Dorf ME, Matsuzawa A, McEvoy LM, Butcher EC. The role of chemokines in the microenvironmental control of T versus B cell arrest in Peyer's patch high endothelial venules. J Exp Med. 2000; 191: 77-88.
Watts DM, Porter KR, Putvatana P, Vasquez B, Calampa C, Hayes CG, Halstead SB. Failure of secondary infection with American genotype dengue 2 to cause dengue haemorrhagic fever. Lancet. 1999; 354: 1431-4.
Weiss SJ, Young J, LoBuglio AF, Slivka A, Nimeh NF. Role of hydrogen peroxide in neutrophil-mediated destruction of cultured endothelial cells. J Clin Invest. 1981; 68: 714-21.
Westwick J, Li SW, Camp RD. Novel neutrophil-stimulating peptides. Immunol Today. 1989; 10: 146-7.
Wong P, Severns CW, Guyer NB, Wright TM. A unique palindromic element mediates gamma interferon induction of mig gene expression. Mol Cell Biol. 1994; 14: 914-22.
Wu SJ, Grouard-Vogel G, Sun W, Mascola JR, Brachtel E, Putvatana R, Louder MK, Filgueira L, Marovich MA, Wong HK, Blauvelt A, Murphy GS, Robb ML, Innes BL, Birx DL, Hayes CG, Frankel SS. Human skin Langerhans cells are targets of dengue virus infection. Nat Med. 2000; 6: 816-20. Yamauchi K, Akber SMF, Horiike N, Michitaka K, Onji M. Increased serum levels of macrophage inflammatory protein-3 alpha in chronic viral hepatitis: prognostic importance of macrophage inflammatory protein-3 alpha during interferon therapy in chronic hepatitis C. Journal of Viral
Hepatitis. 2002; 9: 213-220.
Yoneyama H, Harada A, Imai T, Baba M, Yoshie O, Zhang Y, Higashi H, Murai M, Asakura H, Matsushima K. Pivotal role of TARC, a CC chemokine, in bacteria-induced fulminant hepatic failure in mice. J Clin Invest. 1998; 102: 1933-41.
Yoshie O, Imai T, Nomiyama H. Novel lymphocyte-specific CC chemokines and their receptors. J Leukoc Biol. 1997; 62: 634-44.
