STRUCTURE OF THE HUMAN MACROPHAGE MARCO RECEPTOR AND CHARACTERIZATIONOF ITS BACTERIA-BINDING REGION

The primary structure of human macrophage receptor with collagenous st ructure (MARCO) was determined from cDNA clones and shown to be highly similar to that of mouse (Elomaa, O., Kangas, M., Sahlberg, C., Tuukk anen, J., Sormunen, R., Liakka, A., Thesleff, I., Kraal, G., and Trygg vason, H. (1995) Cell 80, 603-609), Features such as potential carbohy drate attachment sites in the extracellular spacer domain III and the interruption of Gly-Xaa-Yaa repeats in the collagenous domain IV were conserved between the two species, However, the human MARCO polypeptid e chain lacked the intracellular cysteine present in mouse, as well as two extracellular cysteines that form interchain disulfide bonds in t he murine protein, fit situ hybridization showed MARCO to be strongly expressed in macrophages of several tissues of human individuals with sepsis, No expression was observed in other cell types. The bacteria-b inding region of MARCO was determined in binding studies with full-len gth and truncated variants of MARCO, and localized to a region proxima l to the cysteine-rich part of the COOH-terminal domain V, The intrach ain disulfide bond pattern of domain V was established showing that th ese bonds are between cysteine pairs C1-C5, C2-C6, and C3-C4.