Macrophage activation by monosaccharide precursors of Escherichia coli lipid A.
Certain Escherichia coli mutants defective in phosphatidylglycerol biosynthesis accumulate two novel glycolipids, designated X and Y. Lipid X is a diacylglucosamine 1-phosphate bearing beta-hydroxymyristoyl groups at positions 2 and 3, and lipid Y has the same structure as X, except for the additional presence of a palmitoyl moiety on the N-linked beta-hydroxymyristate. We have examined the activities of X, Y, and several related compounds as activators of macrophages. Both X and Y induce morphological changes (spreading), prostaglandin E2 synthesis, and killing of tumor cells by mouse peritoneal macrophages in vitro, properties with which lipopolysaccharide and lipid A are also endowed. Both glycolipids have similar effects on the macrophage-like mouse cell line J774.1. Selective removal from lipid X of either the ester-linked beta-hydroxymyristate at position 3 or the phosphate at position 1 abolishes activity. Our results show that the monosaccharides X and Y retain some of the properties of intact lipopolysaccharide and lipid A with respect to macrophage activation. Because the structures of X and Y are defined, our findings should facilitate the elucidation of the molecular mechanism of macrophage activation by lipid A.
D000818:Animals; D003602:Cytotoxicity, Immunologic; D015232:Dinoprostone; D004926:Escherichia coli / Q000032:analysis*; D006017:Glycolipids / Q000494:pharmacology*; D008050:Lipid A / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects*; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D010461:Peptones / Q000494:pharmacology; D011458:Prostaglandins E / Q000096:biosynthesis
D006017:Glycolipids; D008050:Lipid A; D008070:Lipopolysaccharides; D010461:Peptones; D011458:Prostaglandins E; C044283:lipid X; C044282:lipid Y; D015232:Dinoprostone