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Effects of Androgen Treatment on Expression of Macrophage Fcγ Receptors

机译:雄激素处理对巨噬细胞Fcγ受体表达的影响

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Macrophage Fcγ receptors (FcγRs) play an important role in the host defense against infection and in the pathophysiology of immune cytopenias. Modulation of macrophage FcγR expression is a potential therapeutic approach to immune disorders. Glucocorticoids and progesterones decrease macrophage FcγR expression. We assessed the effect of treatment with androgens and antiandrogens on the expression of macrophage FcγRs using an experimental guinea pig model. Four androgens (testosterone, dihydrotestosterone, mesterolone, and danazol) and five antiandrogens (flutamide, nilutamide, cyproterone acetate, spironolactone, and finasteride) were studied. 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. All of the androgens impaired the clearance of IgG-sensitized erythrocytes by decreasing splenic macrophage FcγR expression. Dihydrotestosterone and mesterolone were more effective than testosterone or dihydrotestosterone. Flow cytometry and fluorescence microscopy with monoclonal antibodies demonstrated that the androgens decreased the cell surface expression of FcγR1,2 more than that of FcγR2. Antiandrogens did not significantly alter macrophage FcγR expression. Nevertheless, antiandrogens counteracted the effects of androgens on macrophage FcγR expression. These data indicate that androgens impair the clearance of IgG-coated cells by decreasing splenic macrophage FcγR expression. Thus, androgens other than danazol are candidate drugs for the treatment of immune disorders.
机译:巨噬细胞Fcγ受体(FcγR)在宿主抵抗感染和免疫性血细胞减少的病理生理中起着重要作用。巨噬细胞FcγR表达的调节是免疫疾病的潜在治疗方法。糖皮质激素和孕激素降低巨噬细胞FcγR表达。我们使用实验性豚鼠模型评估了雄激素和抗雄激素治疗对巨噬细胞FcγRs表达的影响。研究了四个雄激素(睾丸激素,二氢睾丸激素,甲甾醇和达那唑)和五个抗雄激素(氟他胺,尼鲁米特,醋酸环丙孕酮,螺内酯和非那雄胺)。在对豚鼠进行体内治疗后,我们确定了体内免疫球蛋白G(IgG)致敏的红细胞的清除率,IgG致敏的红细胞与脾脏巨噬细胞的分离结合以及脾脏巨噬细胞FcγR细胞表面表达。所有雄激素都通过降低脾脏巨噬细胞FcγR表达来削弱IgG敏感的红细胞的清除。二氢睾丸激素和甲甾醇比睾丸激素或二氢睾丸激素更有效。流式细胞术和单克隆抗体的荧光显微镜检查表明,雄激素比FcγR2减少FcγR1,2的细胞表面表达。抗雄激素没有明显改变巨噬细胞FcγR表达。然而,抗雄激素抵消了雄激素对巨噬细胞FcγR表达的作用。这些数据表明,雄激素通过降低脾巨噬细胞FcγR表达来损害IgG包被的细胞的清除。因此,除达那唑以外的雄激素是用于治疗免疫疾病的候选药物。

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