Characterization of the Murine Macrophage Mannose Receptor: Demonstration That the Downregulation of Receptor Expression Mediated by Interferon-y Occurs at the Level of Transcription

The macrophage mannose receptor (MMR) is a 175-Kd cellsurface transmembrane glycoprotein that is expressed on tissue macrophages where it functions both to mediate the uptake of mannose-rich glycoproteins and as a phagocytic receptor for bacteria, yeasts, and other pathogenic microorganisms. In this report we describe the cloning of the full-length cDNA of the mouse macrophage mannose receptor and we investigate the level at which interferon y (IFN-y) downregulates mannose receptor expression. The latter is a marker of the functional state of the cell as high levels are expressed on resident and inflammatory macrophages, whereas cells activated by treatment with IFNr have decreased-to-absent cell-surface mannose receptor expression. The murine MMR cDNA contains an open reading frame that predicts a protein of 1,456 amino acids. Transient expression of the protein in heterologous cells shows that this cDNA encodes a functional mannose receptor. The deduced amino acid sequence of this protein has an overall 82% homology with the human mannose receptor and as such, the