Roles of a macrophage receptor with collagenous structure (MARCO) in host defense and heterogeneity of splenic marginal zone macrophages

Class A type I and type II macrophage scavenger receptors (MSR-A) and a mac rophage receptor with collagenous structure (MARCO) are trimeric membrane g lycoproteins mediating the uptake of chemically modified low density lipopr oteins. MSR-A is expressed constitutively in several tissue macrophages and in liver sinusoidal endothelial cells, whereas MARCO is expressed constitu tively in splenic marginal zone macrophages and in macrophages and endothel ial cells in the lymphatic medullary sinuses of lymph nodes. The administra tion of LPS, zymosan, BCG, or L. monocytogenes to mice resulted in marked a nd transient MARCO expression and in the upregulation of MSR-A expression i n the liver and spleen. In osteopetrotic (op) mutant mice defective in the production on M-CSF, ER-TRS-positive marginal zone macrophages and MOMA-1-p ositive marginal metallophilic macrophages were absent, whereas MARCO-expre ssing 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 a nd marginal metallophilic macrophages in littermate control mice. In contra st, BCG bacilli were incorporated almost exclusively by MARCO-expressing ma rginal zone macrophages in op/op mice. These results indicate that MARCO is not only expressed constitutively in specific macrophage subpopulations bu t is also induced by various bacterial antigens and plays a role in host de fense against bacteria.