We aimed to reveal the regulatory function of macrophage scavenger receptor-A (MSR-A) in proinflammatory cytokine production by macrophages stimulated with rnycobacterial cord factor (CF). By the culture with CF, MSR-A (+/+) alveolar macrophages and Kupffer cells produced TNF-alpha/MIP-1 alpha 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-1 alpha. production by activated macrophages, suggesting the role of this receptor in suppression of excessive inflammatory responses during mycobacterial infection. (c) 2006 Elsevier Ltd. All rights reserved.