In vitro actions of glucocorticoids on murine macrophages: effects on glucose transport and metabolism, growth in culture, and protein synthesis

Abstract

In vitro exposure of homogeneous monolayer cultures of thioglycollate-elicited mouse peritoneal macrophages to glucocorticoid hormones for up to 96 hr produced a progressive, dose-related inhibition of cell growth and protein synthesis. The reductions in cell protein, incorporation of radiolabeled leucine, and intracellular water space were specific to steroids with glucocorticoid action, with half-maximal inhibition occurring at about 10(-9) M for dexamethasone. Similar dose-related, glucocorticoid-specific decreases in net glucose uptake, lactate production, and 14CO2 production were observed that were only partially explained by the decrease in cell mass. A decrease in the monosaccharide transport system Vmax was also noted but could be completely accounted for by the reduction in cell surface area and the resulting proportional loss in transport sites. No effect on transport system affinity could be demonstrated. The suggestion was made that such long-term culture of macrophages in the presence of glucocorticoids reverses the biochemical and functional changes that comprise the "activated" state of mononuclear phagocytes.