CYTOTOXIC ANTIBODIES TRIGGER INFLAMMATION THROUGH FC-RECEPTORS

Pathogenic self-reactive antibodies are a significant cause of morbidi ty and mortality and contribute to both cytotoxic and immune complex-t riggered inflammatory disorders, typified by rheumatic diseases, autoi mmune hemolytic anemia, and thrombocytopenia. Roles have been proposed for Fc receptors, complement, and complement receptors in the pathoge nesis of these disorders, although the contribution of each to autoimm une injury is unclear. gamma chain-deficient mice lacking Fc gamma RI and Fc gamma RIII are resistant to the development of experimental imm une hemolytic anemia induced by polyclonal rabbit anti-mouse red blood cell IgG antibodies. This resistance is primarily a consequence of in effective erythrophagocytosis, resulting from the lack of Fc gamma Rs on mononuclear phagocytes. Similarly, gamma chain-deficient mice are c ompletely resistant to the development of experimental immune thromboc ytopenia induced by mouse anti-platelet antibodies. These data suggest that Fc receptors play an integral role in the pathogenesis of type I I hypersensitivity and suggest potential therapeutic benefits of Fc re ceptor blockade.