Regulation and functional involvement of macrophage scavenger receptor MARCO in clearance of bacteria in vivo

The scavenger receptors expressed by macrophages are thought to play an imp ortant role in the immune response against bacteria by mediating binding an d phagocytosis. A novel member of the class A scavenger receptor family, ma crophage receptor with collagenous structure (MARCO), has recently been ide ntified. In this study we have generated a panel of mAbs with specificities for different domains of this receptor. Two of those reacting with the C-t erminal cysteine-rich domain block ligand binding of MARCO. The in vivo exp ression of this murine receptor is normally restricted to distinct populati ons of macrophages in the spleen and lymph nodes. During bacillus Calmette- Guerin (BCG) infection, during bacterial sepsis, or after the injection of purified LPS, however, the expression of MARCO is rapidly induced on macrop hages in other tissues, including Kupffer cells in the liver. Using the mou se macrophage cell line J774.2, it was shown that LPS stimulation up regula tes surface expression of MARCO in a dose- and time-dependent fashion. The proinflammatory cytokines IL-1, IL-6, TNF-alpha, and IFN-gamma had little o r no effect. Using inhibitory mAbs, the relevance of MARCO for the clearanc e of circulating bacteria in vivo was determined. Although the overall elim ination of live Escherichia coli and Staphylococcus aureus from the blood d id not appear to be affected by treatment with these Abs, the capturing of heat-killed bacteria by macrophages in the marginal zone areas of the splee n was clearly inhibited. This study suggests a role for MARCO in the host a ntibacterial defense.