Abstract
Splenic-macrophage Fcgamma receptors (FcgammaRs) participate in the pathophysiologies of immune-complex diseases and in host defense against infection. Modulation of macrophage FcgammaR expression is an immuno-therapeutic target. Glucocorticoids, sex steroids, and dopaminergic drugs modulate macrophage FcgammaR expression. Previous data indicate that estradiol increases macrophage FcgammaR expression. Nevertheless, the effects of clinically used estrogens upon macrophage FcgammaR expression are unknown. We assessed the effects of treatment with commonly used estrogens on the expression of macrophage FcgammaRs using a guinea pig experimental model. Six estrogens have been studied: ethynylestradiol (Et), mestranol (M), chlortianisene (Ct), promestriene, 17-epiestriol, and 17beta-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 FcgammaR cell surface expression. Estrogens enhance the clearance of IgG-sensitized erythrocytes by increasing splenic-macrophage FcgammaR 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 FcgammaR1 and -2 more than that of FcgammaR2. These data indicate that treatment with commonly used estrogens enhances the clearance of IgG-sensitized cells by improving splenic-macrophage FcgammaR expression.