Role of macrophage scavenger receptor in endotoxin shock.
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)-1beta expression and serum IL-1beta 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-1beta production by macrophages.
Kobayashi
Y
Y
Second Department of Pathology, Niigata University School of Medicine, Niigata 951-8510, Japan.
Miyaji
C
C
Watanabe
H
H
Umezu
H
H
Hasegawa
G
G
Abo
T
T
Arakawa
M
M
Kamata
N
N
Suzuki
H
H
Kodama
T
T
Naito
M
M
D000818:Animals; D000906:Antibodies / Q000502:physiology; D016207:Cytokines / Q000378:metabolism; D005260:Female; D007375:Interleukin-1 / Q000097:blood / Q000378:metabolism; D008070:Lipopolysaccharides / Q000097:blood / Q000494:pharmacology; D008099:Liver / Q000378:metabolism; D008262:Macrophage Activation / Q000276:immunology / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D011971:Receptors, Immunologic / Q000502:physiology*; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors / Q000502:physiology; D051116:Receptors, Scavenger; D051117:Scavenger Receptors, Class A; D012772:Shock, Septic / Q000097:blood / Q000503:physiopathology*
D000906:Antibodies; D016207:Cytokines; D007375:Interleukin-1; D008070:Lipopolysaccharides; C495140:Msr1 protein, mouse; D011971:Receptors, Immunologic; D017472:Receptors, Interleukin-1; D051116:Receptors, Scavenger; D051117:Scavenger Receptors, Class A