The role of the human Fc receptor Fc gamma RIIA in the immune clearance ofplatelets: A transgenic mouse model

In humans, the Fc receptor for IgG, Fc gamma RIIA, is expressed on macropha ges and platelets and may play an important role in the pathophysiology of immune-mediated thrombocytopenia, Mice lack the genetic equivalent of human Fc gamma RIIA. To better understand the role of Fc gamma RIIA in vivo, Fc gamma RIIA transgenic mice were generated and characterized. One transgenic mouse line expressed Fc gamma RIIA on platelets and macrophages at levels equivalent to human cells, and cross-linking Fc gamma RIIA on these platele ts induced platelet aggregation. Immune-mediated thrombocytopenia in this t ransgenic line was studied using i.v. and i.p. administration of anti-mouse platelet Ab, In comparison with matched wild-type littermates that are neg ative for the Fc gamma RIIA transgene, Ab-mediated thrombocytopenia was sig nificantly more severe in the Fc gamma RIIA transgenic mice. In contrast, F cR gamma-chain knockout mice that lack functional expression of the Fc rece ptors Fc gamma RI and Fc gamma RIII on splenic macrophages did not demonstr ate Ah-mediated thrombocytopenia. We generated Fc gamma RIIA transgenic x F cR gamma-chain knockout mice to examine the role of Fc gamma RIIA in immune clearance in the absence of functional Fc gamma RI and Fc gamma RIII. In F c gamma RIIA transgenic x FcR gamma-chain knockout mice, severe immune thro mbocytopenia mediated by Fc gamma RIIA was observed. These results demonstr ate that Fc gamma RIIA does not require the FcR gamma-chain for expression or function in vivo, Furthermore, taken together, the data suggest that the human Fe receptor Fc gamma RIIA plays a significant role in the immune cle arance of platelets in vivo.