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HIV‐1 Tat‐induced platelet activation and release of CD154 contribute to HIV‐1‐associated autoimmune thrombocytopenia
Author(s) -
WANG J.,
ZHANG W.,
NARDI M. A.,
LI Z.
Publication year - 2011
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/j.1538-7836.2010.04168.x
Subject(s) - platelet activation , platelet , cd154 , immune system , immunology , in vivo , chemistry , cd40 , biology , in vitro , cytotoxic t cell , biochemistry , microbiology and biotechnology
Summary. Background: Enhanced platelet activation in human immunodeficiency virus (HIV)‐1‐infected patients has been reported and shown to strongly correlate with plasma viral load. Activated platelets are known to express and to release a variety of proteins that can modulate the immune system. Specifically, platelet‐derived CD154 has been shown to be directly involved in the development of autoimmune thrombocytopenia (ITP). The mechanism by which HIV‐1 infection leads to platelet activation and the effect of this activation on the development of HIV‐1 ITP, however, is not fully understood. Objective: We have investigated the effect of HIV‐1 Trans activating factor (Tat) on platelet activation. Results: We report that HIV‐1 Tat directly interacts with platelets and induces platelet activation resulting in platelet micro‐particle release. This activation by Tat requires the chemokine receptor CCR3 and β3‐integrin expression on platelets, as well as calcium flux. Tat‐induced activation of platelets releases platelet CD154, an immune modulator. Enhanced B‐cell activity is found in mouse spleen B cells co‐cultured with platelets treated with Tat in vitro . An early antibody response against adenovirus is found in Tat‐injected mouse immunized with adenovirus, suggesting an enhanced immune response in vivo . Conclusions: We have described a role of Tat‐induced platelet activation in the modulation of the immune system, with implications for the development of HIV‐1‐associated thrombocytopenia.