title: CD32-mediated platelet aggregation in vitro by anti-thymocyte globulin: implication of therapy-induced in vivo thrombocytopenia.
abstract: Induction therapy with polyclonal antithymocyte-globulin (ATG) is widely used in the prophylaxis and treatment of acute cardiac-allograft rejection. Thrombocytopenia, however, is a major side-effect of ATG therapy and its mechanisms are poorly understood. The influence of ATG on platelet aggregation was studied aggregometrically, expression of platelet surface activation antigens CD62P and CD63 was determined by flow cytometry analysis, and electron microscopy was utilized to determine thrombocyte morphology. Treatment of platelets with ATG markedly induced aggregation, whereas OKT3 or anti-IL-2R antibodies did not. Furthermore, platelets incubated with ATG featured an up-regulation of the surface activation markers CD62P and CD63, secretion of platelet-bound sCD40L (CD154) and increased signs of aggregation in electron microscopy analysis. The capacity of ATG to induce platelet aggregation was completely blocked by antibodies against the low-affinity Fc IgG receptor (CD32). Since blocking of CD32 abrogates platelet aggregation, we suggest that CD32 plays a crucial role in ATG-induced thrombocytopenia.
authors.affiliation: Department of Cardiothoracic Surgery, University of Vienna, Vienna, Austria. hjankersmit@hotmail.com
authors.forename: Hendrik Jan
authors.initials: HJ
authors.lastname: Ankersmit
authors.forename: Georg Alexander
authors.initials: GA
authors.lastname: Roth
authors.forename: Bernhard
authors.initials: B
authors.lastname: Moser
authors.forename: Andreas
authors.initials: A
authors.lastname: Zuckermann
authors.forename: Markus
authors.initials: M
authors.lastname: Brunner
authors.forename: Christiane
authors.initials: C
authors.lastname: Rosin
authors.forename: Christoph
authors.initials: C
authors.lastname: Buchta
authors.forename: Edith
authors.initials: E
authors.lastname: Bielek
authors.forename: Werner
authors.initials: W
authors.lastname: Schmid
authors.forename: Erika
authors.initials: E
authors.lastname: Jensen-Jarolim
authors.forename: Ernst
authors.initials: E
authors.lastname: Wolner
authors.forename: George
authors.initials: G
authors.lastname: Boltz-Nitulescu
authors.forename: Ivo
authors.initials: I
authors.lastname: Volf
mesh_terms: D005434:Flow Cytometry; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects / Q000276:immunology*; D017452:Receptors, IgG / Q000276:immunology*; D013921:Thrombocytopenia / Q000276:immunology; D013950:Thymus Gland / Q000276:immunology*
chemical_list: D007166:Immunosuppressive Agents; D017452:Receptors, IgG