Molecular characterization of a human scavenger receptor, human MARCO

Murine MARCO has been identified recently in subsets of macrophages located in the peritoneum, marginal zone of the spleen, and the medullary cord of lymph nodes, where it has been proposed that it serves as a bacteria-bindin g receptor. A scavenger receptor family member with an extended collagenous domain, murine MARCO has also been demonstrated in atherosclerotic lesions of susceptible mice. We report here the identification, tissue and chromos omal localization, and pharmacological characterization of human (h)MARCO. hMARCO was identified from a macrophage cDNA library by electronic screenin g with the murine MARCO sequence. Nucleotide sequence analysis confirmed th at the full-length hMARCO clone encoded a 519-amino acid protein sharing 68 .5% identity with murine MARCO. RNA blot analysis indicated that the hMARCO transcript is 2.0 kb in length and is predominantly expressed in human lun g, liver, and lymph nodes. Radiation hybrid mapping localized hMARCO to chr omosome 2q14. Ligand-binding studies of COS cells expressing hMARCO demonst rated significant specific binding of both Escherichia coli and Staphylococ cus aureus. In contrast, the hMARCO receptor expressed in COS cells did not specifically bind the scavenger receptor ligand acetylated low-density lip oprotein (LDL), despite its similarity to the elongated collagen-like bindi ng domain of the macrophage scavenger receptor. In addition, acetylated (Ac )LDL and oxidized (Ox)LDL did not inhibit E. coli binding to hMARCO. These data suggest that hMARCO may play an important role in host defense, but it has no obvious role in the accumulation of modified lipoproteins during at herogenesis.