Gangliosides block the inhibition of macrophage Fc-dependent phagocytosis by lipopolysaccharide.
The mechanism whereby bacterial lipopolysaccharide (LPS) exerts its biologic effects on mammalian cells is unknown. Plasma membrane gangliosides bind bacterial toxins and have been implicated in modulating the effects of a variety of immunoregulatory substances. We investigated the possibility that gangliosides can inhibit the effect of lipopolysaccharide on Fc-dependent phagocytosis by murine peritoneal macrophages. Protein-free lipopolysaccharide preparations significantly inhibited Fc-mediated phagocytosis (less than 71% of control) at concentrations of 100 ng/ml or greater after 90 min of incubation. The inhibitory effect of LPS (1 micrograms/ml) was blocked when macrophages were incubated with mono-, di-, or trisialogangliosides (25-50 micrograms/ml). Neither asialoganglioside nor sialic acid alone were capable of blocking the effect of LPS. When chromatographed separately on a Sepharose 4B column, LPS and trisialoganglioside had different elution profiles. LPS and trisialoganglioside coeluted, however, when premixed at 37 degrees C for 60 min and then applied to the column. Therefore, abrogation of the effect of LPS on Fc-dependent phagocytosis may occur as a consequence of direct interaction between LPS and gangliosides. These data suggest that gangliosides may modulate the response of macrophages to bacterial lipopolysaccharide.
D000818:Animals; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D005732:Gangliosides / Q000494:pharmacology*; D006028:Glycosphingolipids / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors*; D008264:Macrophages / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008815:Mice, Inbred Strains; D010529:Peritoneal Cavity / Q000166:cytology; D010587:Phagocytosis / Q000187:drug effects; D011961:Receptors, Fc / Q000187:drug effects*; D012794:Sialic Acids / Q000494:pharmacology
D005732:Gangliosides; D006028:Glycosphingolipids; D008070:Lipopolysaccharides; D011961:Receptors, Fc; D012794:Sialic Acids