Impaired inflammatory responses in Fc-RIII (CD16) deficient mice

Journal/Book: Z Rheumatol 1998; 57 Suppl. 1: 45 (P 3). 1998;

Abstract: Department of Clinical Immunology Medical School Hannover 1Department of Pathology CMU Geneva Department of Immunology Utrecht Recent work using knock-out mice deficient for the ligand binding (-chain of Fc(RIII demonstrates the critical contribution of Fc(RIII (CD16) in various normal and pathological immunological events. Fc(RIII deficient mice lack NK cell-mediated antibody-dependent cytotoxicity and phagocytosis of IgG1-coated particles by macrophages (1996 Immunity 5: 180 - 188). Fc(RIII deficient mice demonstrate isotype-dependent protection to experimental autoimmune hemolytic anemia indicating an important role of Fc(RIII in the pathogenesis of autoimmune injury (1998 Blood submitted). Strikingly Fc(RIII deficient mice lack IgG-mediated mast cell degranulation are resistant to IgG-dependent passive cutaneous anaphylaxis and exhibit an impaired cutaneous Arthus reaction indicating a prominent role for Fc(RIII in inflammatory and allergic immune responses. The biological significance of diminished type III inflammatory responses was tested in clinical models of alveolitis vasculitis and glomerulonephritis. In the immune complex alveolitis model lung inflammation is attenuated but not completely abrogated in Fc(RIII deficient mice. Strikingly Fc(RIII deficient mice demonstrate complete protection in cryoglobulin-induced skin vasculitis. In contrast the development of nephritis was not significantly affected in Fc(RIII deficient mice compared to their wild-type controls as assessed by disease transfer experiments with bone marrow from male autoimmune BXSB mice. These data demonstrate an important role of Fc(RIII in type III inflammation but also indicate for qualitative differences in distinct disease models. Supported by DFG SFB 265/B01 le

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