Humanized mouse models of FcR clearance in immune platelet disorders

Blood Reviews
Steven E McKenzie

Abstract

Transgenic mouse lines expressing physiologic levels of human platelet Fc receptor (FcR) for IgG, Fc gamma RIIA, on platelets and macrophages were generated. Anti-CD9 antibody activated platelets of Fc gamma RIIA transgenic mice and, following injection in vivo, caused rapid and severe thrombocytopenia compared with nonactivating antiplatelet antibody. Anti-CD9 injected in Fc gamma RIIA transgenic mice crossed with FcR gamma-chain knockout (gamma-KO) mice caused thrombosis and shock in all mice, and death in 16 of 18 mice. Histologic examination of lung vasculature of anti-CD-treated Fc gamma RIIA transgenic x gamma-KO mice showed extensive platelet-fibrin thrombi. Taken together, these observations suggest that in Fc gamma RIIA transgenic x gamma-KO mice there is an important interplay of intravascular platelet activation and splenic clearance. Reduction of splenic clearance surgically or functionally also facilitated anti-CD-9-mediated shock in Fc gamma RIIA transgenic mice. Thus, antibodies that activate platelets in an Fc gamma RIIA-dependent manner lead to thrombosis, shock, and death. These mouse model findings have implications for human immune-mediated thrombocytopenic disorders. Genetic factors may be important in the ...Continue Reading

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Nov 26, 2008·Immunology and Cell Biology·Geoffrey A PieterszP Mark Hogarth
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