Modifications of glycosylation patterns in macrophages upon activation

Abstract

Activated macrophages, in contrast to inflammatory and resident macrophages, are able to inhibit the growth of intracellular pathogens and tumor cells. In order to understand the adaptative changes which allow macrophages to express antitumor activity, we compared, among several parameters, the glycoproteins of cytotoxic and non-cytotoxic macrophages. After activation of mouse peritoneal macrophages by two stimuli applied in a sequence (trehalose dimycolate in vivo, lipopolysaccharide in vitro), we observed that: (1) surface sialic acid residues (labeled by tritiated borohydride after treatment of intact cells in culture by periodate) were reduced by 37%; (2) total sialic acid, as measured by an adaptation to HPLC of the thiobarbituric assay, was reduced by 30%. Variations in the intensity of the labeling after periodate/borohydride treatment were especially pronounced for a few high-molecular-weight glycoproteins. Analysis of glycopeptides indicated that the reduction of sialylation was accompanied by a slight increase in the relative importance of high mannose-type oligosaccharides (glycopeptides sensitive to endoglycosidase H or retained on concanavalin A-Sepharose) but did not affect the ratio of the various anionic species separated on QAE-Sephadex. A reduced sialylation of glycans after activation may facilitate interactions of macrophages with microbes and tumor cells.