Role of macrophage scavenger receptor in endotoxin shock

Lipopolysaccharide (LPS) is known to bind to several receptors on macrophag es, including CD14 and macrophage scavenger receptor class A types I and II (MSR-A), and stimulates macrophages to release various inflammatory mediat ors. MSR-A recognizes a broad range of polyanionic ligands such as chemical ly modified lipoproteins, LPS of Gram-negative bacteria, and lipoteichoic a cid of Gram-positive bacteria, suggesting a role in host defence, In this s tudy, mice lacking MSR-A were used to elucidate the role of MSR-A in endoto xin shock. Peritoneal macrophages from MSR-A-deficient (MSR-A(-/-)) mice bo und less remarkably to LPS than those from wild-type (MSR-A(+/+)) mice and the binding activity of MSR-A(+/+) macrophages to LPS was reduced by the ad dition of an anti-MSR-A antibody. Clearance of LPS in serum was retarded in MSR-A(-/-) mice after intraperitoneal administration of LPS, LPS-induced e xpression of cytokines in the liver was similar in MSR-A(+/+) and MSR-A(-/- ) mice, but levels of interleukin (IL)-1 beta expression and serum IL-1 bet a were lower in MSR-A(-/-) mice, Administration of large doses of LPS resul ted in a higher mortality of MSR-A(+/+) mice and pretreatment with an IL-1 receptor antagonist reduced the mortality. Thus, MSR-A-mediated macrophage activation plays a negative role in protecting mice from endotoxin shock by enhancing IL-1 beta production by macrophages, Copyright (C) 2000 John Wil ey & Sons, Ltd.