Roles of a Macrophage Receptor with Collagenous Structure (MARCO) in Host Defense and Heterogeneity of Splenic Marginal Zone Macrophages

Abstract

Class A type I and type II macrophage scavenger receptors (MSR-A) and a macrophage receptor with collagenous structure (MARCO) are trimeric membrane glycoproteins mediating the uptake of chemically modified low density lipoproteins. MSR-A is expressed constitutively in several tissue macrophages and in liver sinusoidal endothelial cells, whereas MARCO is expressed constitutively in splenic marginal zone macrophages and in macrophages and endothelial cells in the lymphatic medullary sinuses of lymph nodes. The administration of LPS, zymosan, BCG, or L. monocytogenes to mice resulted in marked and transient MARCO expression and in the upregulation of MSR-A expression in the liver and spleen. In osteopetrotic (op) mutant mice defective in the production on M-CSF, ER-TR9-positive marginal zone macrophages and MOMA-1-positive marginal metallophilic macrophages were absent, whereas MARCO-expressing marginal zone macrophages were present, indicating the heterogeneity of marginal zone macrophages. Intravenous administration of BCG resulted in marked accumulation of BCG bacilli in the both marginal zone macrophages and marginal metallophilic macrophages in littermate control mice. In contrast, BCG bacilli were incorporated almost exclusively by MARCO-expressing marginal zone macrophages in op/op mice. These results indicate that MARCO is not only expressed constitutively in specific macrophage subpopulations but is also induced by various bacterial antigens and plays a role in host defense against bacteria.