The role of the human Fc receptor Fc gamma RIIA in the immune clearance of platelets: a transgenic mouse model.

作者：Steven Edward McKenzie, Stephen M. Taylor, Padmini Malladi, Heena Yuhan, Diana L. Cassel, Paul T. Chien, Elias Schwartz, AD Schreiber, Saul Surrey, Muredach P. Reilly · 发表于：PubMed · 年份：1999 · 被引用次数：185 · 研究领域：Monoclonal and Polyclonal Antibodies Research、Platelet Disorders and Treatments、Glycosylation and Glycoproteins Research

In humans, the Fc receptor for IgG, FcgammaRIIA, is expressed on macrophages and platelets and may play an important role in the pathophysiology of immune-mediated thrombocytopenia. Mice lack the genetic equivalent of human FcgammaRIIA. To better understand the role of FcgammaRIIA in vivo, FcgammaRIIA transgenic mice were generated and characterized. One transgenic mouse line expressed FcgammaRIIA on platelets and macrophages at levels equivalent to human cells, and cross-linking FcgammaRIIA on these platelets induced platelet aggregation. Immune-mediated thrombocytopenia in this transgenic line was studied using i.v. and i.p. administration of anti-mouse platelet Ab. In comparison with matched wild-type littermates that are negative for the FcgammaRIIA transgene, Ab-mediated thrombocytopenia was significantly more severe in the FcgammaRIIA transgenic mice. In contrast, FcR gamma-chain knockout mice that lack functional expression of the Fc receptors FcgammaRI and FcgammaRIII on splenic macrophages did not demonstrate Ab-mediated thrombocytopenia. We generated FcgammaRIIA transgenic x FcR gamma-chain knockout mice to examine the role of FcgammaRIIA in immune clearance in the absence of functional FcgammaRI and FcgammaRIII. In FcgammaRIIA transgenic x FcR gamma-chain knockout mice, severe immune thrombocytopenia mediated by FcgammaRIIA was observed. These results demonstrate that FcgammaRIIA does not require the FcR gamma-chain for expression or function in vivo. Furthermore, ...