Differential effect of Fc gamma receptor ligation on LPS-stimulated TNF-alpha secretion by hepatic, splenic, and peritoneal macrophages.

Abstract

Lipopolysaccharide (LPS) increases serum TNF-alpha levels due to TNF-alpha secretion by macrophages. The serum TNF-alpha response to LPS was augmented 10x when FcgammaR ligation was induced by the intravenous injection of Gig-coated erythrocytes (IgG) prior to the administration of LPS. The macrophage population responsible for the augmented TNF-alpha secretion was determined by isolating Kupffer cells, splenic macrophages and peritoneal macrophages from mice that had been given ElgG prior to LPS and determining TNF-alpha secretion ex vivo. The intravenous injection of ElgG augmented LPS-stimulate TNF-alpha secretion by Kupffer cells and splenic macrophages. In contrast, LPS-stimulated TNF-alpha secretion by peritoneal macrophages was not altered by either the intravenous or intraperitoneal injection of ElgG. In vitro phagocytosis of ElgG by isolated peritoneal macrophages also did not augment LPS-stimulated TNF-alpha secretion. These results show that FcgammaR ligation augments LPS-stimulated TNF-alpha secretion by Kupffer cells and splenic macrophages but not by peritoneal macrophages. Thus, the ability of FcgammaR ligation to influence TNF-alpha secretion may be specific to the tissue source of the macrophages.