Enhancement of Splenic-Macrophage Fcγ Receptor Expression by Treatment with Estrogens

Abstract

ABSTRACT Splenic-macrophage Fcγ receptors (FcγRs) participate in the pathophysiologies of immune-complex diseases and in host defense against infection. Modulation of macrophage FcγR expression is an immuno-therapeutic target. Glucocorticoids, sex steroids, and dopaminergic drugs modulate macrophage FcγR expression. Previous data indicate that estradiol increases macrophage FcγR expression. Nevertheless, the effects of clinically used estrogens upon macrophage FcγR expression are unknown. We assessed the effects of treatment with commonly used estrogens on the expression of macrophage FcγRs using a guinea pig experimental model. Six estrogens have been studied: ethynylestradiol (Et), mestranol (M), chlortianisene (Ct), promestriene, 17-epiestriol, and 17β-estradiol. Following in vivo treatment of guinea pigs, we determined the clearance of immunoglobulin G (IgG)-sensitized erythrocytes in vivo, the binding of IgG-sensitized erythrocytes by isolated splenic macrophages, and splenic-macrophage FcγR cell surface expression. Estrogens enhance the clearance of IgG-sensitized erythrocytes by increasing splenic-macrophage FcγR expression. Et, M, and Ct were more effective than the other estrogens. Flow cytometry and fluorescence microscopy with monoclonal antibodies demonstrated that estrogens increase the cell surface expression of FcγR1 and -2 more than that of FcγR2. These data indicate that treatment with commonly used estrogens enhances the clearance of IgG-sensitized cells by improving splenic-macrophage FcγR expression.