Macrophage scavenger receptor down-regulates mycobacterial cord factor-induced proinflammatory cytokine production by alveolar and hepatic macrophages.
We aimed to reveal the regulatory function of macrophage scavenger receptor-A (MSR-A) in proinflammatory cytokine production by macrophages stimulated with mycobacterial cord factor (CF). By the culture with CF, MSR-A (+/+) alveolar macrophages and Kupffer cells produced TNF-alpha/MIP-1alpha in a time- and dose-dependent manner. However, the amounts of cytokines produced by them were much less compared to those produced by MSR-A (-/-) macrophages. Consistent with this, treatment of MSR-A (+/+) macrophages with anti-MSR-A antibody increased TNF-alpha production. Binding of CF to MSR-A was demonstrated by measuring the binding affinity. These results indicate that CF binds MSR-A, and MSR-A down-regulates TNF-alpha/MIP-1alpha production by activated macrophages, suggesting the role of this receptor in suppression of excessive inflammatory responses during mycobacterial infection.
Ozeki
Yuriko
Y
Department of Host Defense, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan. yuriozeki@med.osaka-cu.ac.jp
Tsutsui
Hiroko
H
Kawada
Norifumi
N
Suzuki
Hiroshi
H
Kataoka
Motoyuki
M
Kodama
Tatsuhiko
T
Yano
Ikuya
I
Kaneda
Kenji
K
Kobayashi
Kazuo
K
D000818:Animals; D054407:Chemokine CCL4; D003311:Cord Factors / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism*; D015536:Down-Regulation; D007728:Kupffer Cells / Q000276:immunology*; D008262:Macrophage Activation; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000276:immunology*; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000276:immunology / Q000378:metabolism; D051117:Scavenger Receptors, Class A / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D054407:Chemokine CCL4; D003311:Cord Factors; D016207:Cytokines; D019402:Macrophage Inflammatory Proteins; C495140:Msr1 protein, mouse; D051117:Scavenger Receptors, Class A; D014409:Tumor Necrosis Factor-alpha