title: HIV-1 Tat-induced platelet activation and release of CD154 contribute to HIV-1-associated autoimmune thrombocytopenia.
abstract: 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.
authors.affiliation: Department of Medicine, NYU Cancer Institute, New York, NY 10016, USA.
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.forename: W
authors.initials: W
authors.lastname: Zhang
authors.forename: M A
authors.initials: MA
authors.lastname: Nardi
authors.forename: Z
authors.initials: Z
authors.lastname: Li
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D001792:Blood Platelets / Q000276:immunology / Q000648:ultrastructure; D023201:CD40 Ligand / Q000097:blood* / Q000172:deficiency / Q000235:genetics; D020013:Calcium Signaling; D002460:Cell Line; D055252:Cell-Derived Microparticles / Q000648:ultrastructure; D000242:Cyclic AMP / Q000097:blood; D015756:Genes, tat; D015658:HIV Infections / Q000097:blood / Q000150:complications* / Q000276:immunology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity*; D006801:Humans; D039661:Integrin beta3 / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D008954:Models, Biological; D015539:Platelet Activation; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000097:blood / Q000209:etiology* / Q000276:immunology / Q000821:virology; D054397:Receptors, CCR3 / Q000097:blood; D014162:Transfection; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*
chemical_list: C515350:CCR3 protein, human; D039661:Integrin beta3; D054397:Receptors, CCR3; D054322:tat Gene Products, Human Immunodeficiency Virus; D023201:CD40 Ligand; D000242:Cyclic AMP