Anti-dengue virus nonstructural protein 1 antibodies contribute to platelet phagocytosis by macrophages

Shu Wen Wan, Yi Wen Yang, Ya Ting Chu, Chiou Feng Lin, Chih Peng Chang, Trai Ming Yeh, Robert Anderson, Yee Shin Lin

研究成果: Article

10 引文 (Scopus)

摘要

Thrombocytopenia is an important clinical manifestation of dengue disease. The hypotheses concerning the pathogenesis of thrombocytopenia include decreased production and increased destruction or consumption of platelets. We previously suggested a mechanism of molecular mimicry in which antibodies (Abs) directed against dengue virus (DENV) nonstructural protein 1 (NS1) cross-react with platelets. Furthermore, several lines of evidence show activation of endothelial cells (ECs) and macrophages are related to dengue disease severity. Previous studies also suggested that Ab-opsonised platelets facilitate the engulfment of platelets by macrophages. Here we show that TNFα-activated ECs upregulate adhesion molecule expression to enhance the binding of platelets and macrophages and lead to anti-DENV NS1 Ab-mediated platelet phagocytosis. We further demonstrate that the interaction between macrophages and TNF-α-activated ECs requires binding of FcγR with the Fc region of platelet-bound anti-DENV NS1 Abs. Importantly, the binding of anti-DENV NS1 Abs to platelets did not interfere with platelet adhesion to ECs. The adhesion molecules ICAM-1 and β3 integrin expressed on ECs as well as the FcγR expressed on macrophages were critical in anti-DENV NS1 Ab-mediated platelet phagocytosis on activated ECs. Moreover, anti-DENV NS1 Abs dramatically enhanced platelet engulfment by macrophages in a murine model of DENV infection. Our study provides evidence for a novel role for anti-DENV NS1 Abs in the pathogenesis of thrombocytopenia in dengue disease by enhancing platelet phagocytosis by macrophages.

原文English
頁(從 - 到)646-656
頁數11
期刊Thrombosis and Haemostasis
115
發行號3
DOIs
出版狀態Published - 2016 一月 1

指紋

Dengue Virus
Phagocytosis
Blood Platelets
Macrophages
Antibodies
Proteins
Endothelial Cells
Dengue
Thrombocytopenia
Cell Adhesion Molecules
Molecular Mimicry
Virus Diseases
Intercellular Adhesion Molecule-1
Integrins
Up-Regulation

All Science Journal Classification (ASJC) codes

  • Hematology

引用此文

Wan, Shu Wen ; Yang, Yi Wen ; Chu, Ya Ting ; Lin, Chiou Feng ; Chang, Chih Peng ; Yeh, Trai Ming ; Anderson, Robert ; Lin, Yee Shin. / Anti-dengue virus nonstructural protein 1 antibodies contribute to platelet phagocytosis by macrophages. 於: Thrombosis and Haemostasis. 2016 ; 卷 115, 編號 3. 頁 646-656.
@article{07e5bd22433944f7b2b8ffaad59b8e5c,
title = "Anti-dengue virus nonstructural protein 1 antibodies contribute to platelet phagocytosis by macrophages",
abstract = "Thrombocytopenia is an important clinical manifestation of dengue disease. The hypotheses concerning the pathogenesis of thrombocytopenia include decreased production and increased destruction or consumption of platelets. We previously suggested a mechanism of molecular mimicry in which antibodies (Abs) directed against dengue virus (DENV) nonstructural protein 1 (NS1) cross-react with platelets. Furthermore, several lines of evidence show activation of endothelial cells (ECs) and macrophages are related to dengue disease severity. Previous studies also suggested that Ab-opsonised platelets facilitate the engulfment of platelets by macrophages. Here we show that TNFα-activated ECs upregulate adhesion molecule expression to enhance the binding of platelets and macrophages and lead to anti-DENV NS1 Ab-mediated platelet phagocytosis. We further demonstrate that the interaction between macrophages and TNF-α-activated ECs requires binding of FcγR with the Fc region of platelet-bound anti-DENV NS1 Abs. Importantly, the binding of anti-DENV NS1 Abs to platelets did not interfere with platelet adhesion to ECs. The adhesion molecules ICAM-1 and β3 integrin expressed on ECs as well as the FcγR expressed on macrophages were critical in anti-DENV NS1 Ab-mediated platelet phagocytosis on activated ECs. Moreover, anti-DENV NS1 Abs dramatically enhanced platelet engulfment by macrophages in a murine model of DENV infection. Our study provides evidence for a novel role for anti-DENV NS1 Abs in the pathogenesis of thrombocytopenia in dengue disease by enhancing platelet phagocytosis by macrophages.",
author = "Wan, {Shu Wen} and Yang, {Yi Wen} and Chu, {Ya Ting} and Lin, {Chiou Feng} and Chang, {Chih Peng} and Yeh, {Trai Ming} and Robert Anderson and Lin, {Yee Shin}",
year = "2016",
month = "1",
day = "1",
doi = "10.1160/TH15-06-0498",
language = "English",
volume = "115",
pages = "646--656",
journal = "Thrombosis and Haemostasis",
issn = "0340-6245",
publisher = "Schattauer GmbH",
number = "3",

}

Anti-dengue virus nonstructural protein 1 antibodies contribute to platelet phagocytosis by macrophages. / Wan, Shu Wen; Yang, Yi Wen; Chu, Ya Ting; Lin, Chiou Feng; Chang, Chih Peng; Yeh, Trai Ming; Anderson, Robert; Lin, Yee Shin.

於: Thrombosis and Haemostasis, 卷 115, 編號 3, 01.01.2016, p. 646-656.

研究成果: Article

TY - JOUR

T1 - Anti-dengue virus nonstructural protein 1 antibodies contribute to platelet phagocytosis by macrophages

AU - Wan, Shu Wen

AU - Yang, Yi Wen

AU - Chu, Ya Ting

AU - Lin, Chiou Feng

AU - Chang, Chih Peng

AU - Yeh, Trai Ming

AU - Anderson, Robert

AU - Lin, Yee Shin

PY - 2016/1/1

Y1 - 2016/1/1

N2 - Thrombocytopenia is an important clinical manifestation of dengue disease. The hypotheses concerning the pathogenesis of thrombocytopenia include decreased production and increased destruction or consumption of platelets. We previously suggested a mechanism of molecular mimicry in which antibodies (Abs) directed against dengue virus (DENV) nonstructural protein 1 (NS1) cross-react with platelets. Furthermore, several lines of evidence show activation of endothelial cells (ECs) and macrophages are related to dengue disease severity. Previous studies also suggested that Ab-opsonised platelets facilitate the engulfment of platelets by macrophages. Here we show that TNFα-activated ECs upregulate adhesion molecule expression to enhance the binding of platelets and macrophages and lead to anti-DENV NS1 Ab-mediated platelet phagocytosis. We further demonstrate that the interaction between macrophages and TNF-α-activated ECs requires binding of FcγR with the Fc region of platelet-bound anti-DENV NS1 Abs. Importantly, the binding of anti-DENV NS1 Abs to platelets did not interfere with platelet adhesion to ECs. The adhesion molecules ICAM-1 and β3 integrin expressed on ECs as well as the FcγR expressed on macrophages were critical in anti-DENV NS1 Ab-mediated platelet phagocytosis on activated ECs. Moreover, anti-DENV NS1 Abs dramatically enhanced platelet engulfment by macrophages in a murine model of DENV infection. Our study provides evidence for a novel role for anti-DENV NS1 Abs in the pathogenesis of thrombocytopenia in dengue disease by enhancing platelet phagocytosis by macrophages.

AB - Thrombocytopenia is an important clinical manifestation of dengue disease. The hypotheses concerning the pathogenesis of thrombocytopenia include decreased production and increased destruction or consumption of platelets. We previously suggested a mechanism of molecular mimicry in which antibodies (Abs) directed against dengue virus (DENV) nonstructural protein 1 (NS1) cross-react with platelets. Furthermore, several lines of evidence show activation of endothelial cells (ECs) and macrophages are related to dengue disease severity. Previous studies also suggested that Ab-opsonised platelets facilitate the engulfment of platelets by macrophages. Here we show that TNFα-activated ECs upregulate adhesion molecule expression to enhance the binding of platelets and macrophages and lead to anti-DENV NS1 Ab-mediated platelet phagocytosis. We further demonstrate that the interaction between macrophages and TNF-α-activated ECs requires binding of FcγR with the Fc region of platelet-bound anti-DENV NS1 Abs. Importantly, the binding of anti-DENV NS1 Abs to platelets did not interfere with platelet adhesion to ECs. The adhesion molecules ICAM-1 and β3 integrin expressed on ECs as well as the FcγR expressed on macrophages were critical in anti-DENV NS1 Ab-mediated platelet phagocytosis on activated ECs. Moreover, anti-DENV NS1 Abs dramatically enhanced platelet engulfment by macrophages in a murine model of DENV infection. Our study provides evidence for a novel role for anti-DENV NS1 Abs in the pathogenesis of thrombocytopenia in dengue disease by enhancing platelet phagocytosis by macrophages.

UR - http://www.scopus.com/inward/record.url?scp=84964766245&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84964766245&partnerID=8YFLogxK

U2 - 10.1160/TH15-06-0498

DO - 10.1160/TH15-06-0498

M3 - Article

C2 - 26632672

AN - SCOPUS:84964766245

VL - 115

SP - 646

EP - 656

JO - Thrombosis and Haemostasis

JF - Thrombosis and Haemostasis

SN - 0340-6245

IS - 3

ER -