A Mannose Receptor Mediates Mannosyl-rich Glycoprotein-induced Mitogenesis in Bovine Airway Smooth Muscle Cells

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The putative mannose receptor (MR), previously implicated in mannosyl-rich glycoprotein-induced mitogenesis in bovine airway smooth muscle (ASM) cells, was studied to determine its properties. Specific binding of the mitogenic neoglycoprotein, mannosylated bovine serum albumin (ManBSA) to ASM cells was saturable, with an apparent Kd = 5.0 x 10-8 M. Cell-bound ManBSA-colloidal gold conjugate was localized by electron microscopy to clathrin-coated pits on the cell surface, and was found to undergo internalization to endosomes; this was inhibitable by weak bases and swainsonine, that also inhibited ligand-induced mitogenesis. The ASM-MR, isolated by mannose-affinity chromatography, had the same apparent molecular mass as the macrophage (Mo) MR (Mr = 175 kD), and was immunoprecipitated by an anti-MoMR immune serum. This antiserum blocked Iodine-125-labeled-ManBSA binding to intact ASM cells, stimulated mitogenesis, and immunolocalized the ASM-MR in cytoplasmic vesicles compatible with endosomes. A monoclonal antibody directed against the MoMR also reacted with the ASM-MR; like the polyclonal antibodies, it stimulated mitogenesis as effectively as beta-hexosaminidases. These data indicate that the ASM-MR shares a number of functional and structural properties with the MoMR and suggest that similar receptors may have different main functions in different cells. (J. Clin. Invest. 1994. 94:1855-1863.) Key words: airway smooth muscle. proliferation. agonistic antibodies. lysosomal hydrolases. asthma

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