Suppression of yeast ingestion by dexamethasone in macrophage cultures: Evidence for a steroid-induced phagocytosis inhibitory protein

Abstract

The mechanism by which glucocorticoid steroids suppress yeast phagocytosis in cultures of resident and thioglycollate-elicited murine peritoneal macrophages was examined. Time course and dose-response studies demonstrated that the phagocytic capacity of resident macrophages was suppressed by dexamethasone to the same extent in both newly established cultures and cultures that were incubated for several days. In contrast, relative to newly established cultures of elicited cells that were treated with the drug, elicited macrophages that were incubated for at least 1 day prior to exposure to dexamethasone, exhibited enhanced sensitivity to the action of the steroid. Steroid-induced phagocytic inhibitory responses were blocked by the metabolic inhibitors cycloheximide and actinomycin D. The suppression of phagocytosis by dexamethasone was mediated by a factor, present in the cellular homogenates of steroid-treated macrophages, that was partially purified by Sephadex G-25 chromatography. Since the phagocytic inhibitory activity in these homogenates was destroyed following exposure to heat and trypsin, the factor has been named phagocytosis inhibitory protein (PIP). The antiphagocytic activity of PIP was neutralized by treatment with RM23, a monoclonal antibody directed against lipocortin. These results support the hypothesis that the suppression of yeast ingestion is mediated by the action of PIP, which is induced in dexamethasone-treated macrophage cultures. Moreover, PIP appears to belong to the lipocortin family of phospholipase inhibitory proteins.