Treatment with progesterone analogues decreases macrophage Fcγ receptors expression

Macrophage Fc gamma receptors (Fc gamma Rs) are critical for host defense against infection and have an important role in immune cytopenias. Modulation of macrophage Fc gamma Rs expression is a potential therapeutic approach to immune disorders. Glucocorticoids and synthetic progesterone analogues decrease macrophage Fc gamma Rs expression. We assessed the effect of treatment with commonly employed progestins on the expression of macrophage Fc gamma Rs using an experimental model in the guinea pig. Eight clinically available progesterones, medroxyprogesterone acetate (P3), megestrol acetate (P4), medrogestone (P5), alylestrenol (P6), line-strenol (P7), didrogesterone (P8), norethisterone (P9), and gestonorone caproate (P10) and two endogenous progesterones, progesterone (P1) and lr alpha-hydroxyprogesterone (P2), were studied. Following in vivo treatment of guinea pigs, we determined the clearance of IgG-sensitized erythrocytes in vivo, the binding of IgG-sensitized erythrocytes by isolated splenic macrophages, and splenic macrophage Fc gamma receptor cell surface expression. All progesterones impaired the clearance of IgG-sensitized erythrocytes by decreasing splenic macrophage Fc gamma receptor expression. P5, P6, P7, and P8 were less effective. Flow cytometry and fluorescence microscopy with monoclonal antibodies demonstrated that progesterones decreased the cell surface expression of Fc gamma R2 more than that of Fc gamma R1,2. Clinically employed progestins impair the clearance of IgG-coated cells by decreasing splenic macrophage Fc gamma Rs expression. Thus, progesterones are candidate drugs for the treatment of immune disorders. (C) 1998 Academic Press.