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RIIA in the Immune Clearance of Platelets: A Transgenic Mouse Model1
*
Department of Pediatrics, Jefferson Medical College, Philadelphia, PA 19107, and Hematology/Oncology Research, Alfred I. duPont Hospital for Children, Wilmington, DE 19899; and
Division of Hematology/Oncology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104
In humans, the Fc receptor for IgG, Fc
RIIA, 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 FcRIIA. To better understand the role of
FcRIIA in vivo, FcRIIA transgenic mice were generated and
characterized. One transgenic mouse line expressed FcRIIA on
platelets and macrophages at levels equivalent to human cells, and
cross-linking FcRIIA 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 FcRIIA transgene, Ab-mediated thrombocytopenia was
significantly more severe in the FcRIIA transgenic mice. In
contrast, FcR -chain knockout mice that lack functional expression
of the Fc receptors FcRI and FcRIII on splenic macrophages did
not demonstrate Ab-mediated thrombocytopenia. We generated FcRIIA
transgenic x FcR -chain knockout mice to examine the role of
FcRIIA in immune clearance in the absence of functional FcRI and
FcRIII. In FcRIIA transgenic x FcR -chain knockout mice,
severe immune thrombocytopenia mediated by FcRIIA was observed.
These results demonstrate that FcRIIA does not require the FcR
-chain for expression or function in vivo. Furthermore, taken
together, the data suggest that the human Fc receptor FcRIIA plays a
significant role in the immune clearance of platelets in
vivo.
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