Comparative effects of Mycobacterium avium glycopeptidolipid and lipopeptide fragment on the function and ultrastructure of mononuclear cells.

Among the various lipids associated with the cell envelope of the Mycobacterium avium complex, the species-specific glycopeptidolipids (GPL) are responsible for distinguishing one serovar from another. In a continuing effort to study the immunomodulatory capabilities of these mycobacterial lipids, we have examined and compared the effects of the GPL and its lipopeptide fragment (beta-lipid) on mononuclear cell function. It was observed that the lymphoproliferative response of murine splenic mononuclear cells to mitogen stimulation was reduced by both the GPL and its lipopeptide fragment. Although the responsiveness appeared to be down-regulated to a greater degree by the beta-lipid, treatment with either GPL or beta-lipid resulted in the release of soluble factors from peritoneal macrophages that caused suppression of the lymphoproliferative responsiveness of splenic mononuclear cells. Flow cytometric analysis of peritoneal macrophages revealed that treatment with the beta-lipid fragment caused a marked decrease in expression of the C3bi complement receptor, Mac-1, on macrophages, whereas treatment with GPL resulted in a marked increase in the expression of Mac-2 receptor on macrophages. Treatment of peritoneal macrophages with either GPL or beta-lipid resulted in the release of tumour necrosis factor (TNF), as determined by an L929 biological cytotoxicity assay. Perturbation of macrophage membrane ultrastructure by both GPL and beta-lipid was confirmed by electron microscopy, and may be a possible explanation for the resulting alterations in mononuclear cell function observed in this study.