Treatment with Progesterone Analogues Decreases Macrophage Fcγ Receptors Expression

Abstract

Macrophage Fcγ receptors (FcγRs) are critical for host defense against infection and have an important role in immune cytopenias. Modulation of macrophage FcγRs expression is a potential therapeutic approach to immune disorders. Glucocorticoids and synthetic progesterone analogues decrease macrophage FcγRs expression. We assessed the effect of treatment with commonly employed progestins on the expression of macrophage FcγRs using an experimental model in the guinea pig. Eight clinically available progesterones, medroxyprogesterone acetate (P3), megestrol acetate (P4), medrogestone (P5), alylestrenol (P6), linestrenol (P7), didrogesterone (P8), norethisterone (P9), and gestonorone caproate (P10) and two endogenous progesterones, progesterone (P1) and 17 α-hydroxyprogesterone (P2), were studied. Followingin vivotreatment of guinea pigs, we determined the clearance of IgG-sensitized erythrocytesin vivo,the binding of IgG-sensitized erythrocytes by isolated splenic macrophages, and splenic macrophage Fcγ receptor cell surface expression. All progesterones impaired the clearance of IgG-sensitized erythrocytes by decreasing splenic macrophage Fcγ 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 FcγR2 more than that of FcγR1,2. Clinically employed progestins impair the clearance of IgG-coated cells by decreasing splenic macrophage FcγRs expression. Thus, progesterones are candidate drugs for the treatment of immune disorders.