Role of macrophage scavenger receptor in endotoxin shock

Abstract

Lipopolysaccharide (LPS) is known to bind to several receptors on macrophages, including CD14 and macrophage scavenger receptor class A types I and II (MSR-A), and stimulates macrophages to release various inflammatory mediators. MSR-A recognizes a broad range of polyanionic ligands such as chemically modified lipoproteins, LPS of Gram-negative bacteria, and lipoteichoic acid of Gram-positive bacteria, suggesting a role in host defence. In this study, mice lacking MSR-A were used to elucidate the role of MSR-A in endotoxin shock. Peritoneal macrophages from MSR-A-deficient (MSR-A−/−) mice bound 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 addition of an anti-MSR-A antibody. Clearance of LPS in serum was retarded in MSR-A−/− mice after intraperitoneal administration of LPS. LPS-induced expression of cytokines in the liver was similar in MSR-A+/+ and MSR-A−/− mice, but levels of interleukin (IL)-1β expression and serum IL-1β were lower in MSR-A−/− mice. Administration of large doses of LPS resulted 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-1β production by macrophages. Copyright © 2000 John Wiley & Sons, Ltd.