title: Cytotoxic antibodies trigger inflammation through Fc receptors.
abstract: Pathogenic self-reactive antibodies are a significant cause of morbidity and mortality and contribute to both cytotoxic and immune complex-triggered inflammatory disorders, typified by rheumatic diseases, autoimmune hemolytic anemia, and thrombocytopenia. Roles have been proposed for Fc receptors, complement, and complement receptors in the pathogenesis of these disorders, although the contribution of each to autoimmune injury is unclear. gamma chain-deficient mice lacking Fc gamma RI and Fc gamma RIII are resistant to the development of experimental immune hemolytic anemia induced by polyclonal rabbit anti-mouse red blood cell IgG antibodies. This resistance is primarily a consequence of ineffective erythrophagocytosis, resulting from the lack of Fc gamma Rs on mononuclear phagocytes. Similarly, gamma chain-deficient mice are completely resistant to the development of experimental immune thrombocytopenia induced by mouse anti-platelet antibodies. These data suggest that Fc receptors play an integral role in the pathogenesis of type II hypersensitivity and suggest potential therapeutic benefits of Fc receptor blockade.
authors.affiliation: Program in Molecular Biology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
authors.forename: R
authors.initials: R
authors.lastname: Clynes
authors.forename: J V
authors.initials: JV
authors.lastname: Ravetch
mesh_terms: D000743:Anemia, Hemolytic / Q000276:immunology*; D000818:Animals; D000906:Antibodies / Q000008:administration & dosage; D003602:Cytotoxicity, Immunologic; D004912:Erythrocytes / Q000276:immunology; D008099:Liver / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D011961:Receptors, Fc / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D013921:Thrombocytopenia / Q000276:immunology*
chemical_list: D000906:Antibodies; D011961:Receptors, Fc