Endogenous ligands of carbohydrate recognition domains of the mannose receptor in murine macrophages, endothelial cells and secretory cells; potential relevance to inflammation and immunity

The macrophage mannose receptor (MR) has an established role in the phagocy tosis of a wide range of microbes, and also functions in Viral endocytosis, and clearance of a number of endogenous glycoproteins from the circulation . Its broad ligand specificity is mediated by tandemly linked carbohydrate recognition domains (CRDs). Recent studies suggest that binding or internal ization of both natural and synthetic ligands of MR CRDs may modulate macro phage (M phi) function, for example to increase cidal capacity or cytokine synthesis. To identify endogenous ligands in the normal mouse we used an Fc -fusion protein (CRD4-7Fc) bearing four of the CRDs of MR. CRD4-7Fc recogni zed endocytic compartments of cultured M phi, consistent with lysosomal enz ymes being major ligands of MR. CRD4-7Fc also recognized M phi and some end othelial cells in tissues, and intensely labeled secretory cells of the exo crine pancreas, salivary gland and thyroid. Strongly MR-positive interstiti al cells were found in close proximity to the ligand-rich secretory cells, suggesting a role for MR in uptake of secretory glycoproteins, including th yroglobulin which was identified as a novel ligand in vitro. Endocytosis of these ligands by MR may have implications for tissue homeostasis and immun ity, including antigen presentation, in secretory organs.