Down regulation of macrophage mannose/N-acetylglucosamine receptors by elevated glucose concentrations

The binding of the 125I-induced neoglycoprotein mannosyl-bovine serum albumin (Man-albumin) to peptone-elicited murine peritoneal macrophages was examined. Binding studies demonstrated that the extent of receptor activity for Man-albumin depended upon the glucose concentration of the medium in which the cells were cultured following peritoneal lavage and prior to the binding assay. Macrophages cultured in a medium containing a high glucose concentration (25 mM or greater) prior to the binding assay, consistently showed a reduced capacity for binding Man-albumin as compared to cells cultured in the presence of low glucose (5 mM). These results were obtained in a variety of tissue culture media or when the same medium was employed with differing amounts of added glucose (5, 25 and 50 mM). Cell toxicity and/or death was not the cause of the reduced receptor activity of macrophages cultured in high glucose as determined by morphology. Trypan blue exclusion, and the ability of these cells to actively phagocytose IgG-coated sheep red blood cells to an extent identical with those cells cultured in low glucose. Saturation binding studies and Scatchard analysis of the data demonstrated that the decreased level of binding observed with cells cultured in high glucose was the result of a reduced number of receptors and not altered receptor affinity. These studies suggest that an increased glucose concentration, such as in diabetes mellitus, can downshift the expression of the mannose/N-acetylglucosamine receptor on murine peritoneal macrophages.