A monosaccharide precursor of Escherichia coli lipid A has the ability to induce tumor-cytotoxic factor production by a murine macrophage-like cell line, J774.1.
A monosaccharide precursor of Escherichia coli lipid A, designated lipid X, which is a diacylglucosamine 1-phosphate with beta-hydroxymyristoyl groups at positions 2 and 3, was shown to have the ability to induce the production of tumor necrosis factor (TNF)-like tumor-cytotoxic factor by a murine macrophage-like cell line, J774.1. This cytotoxic factor was released from J774.1 cells grown in the presence of lipid X and related compounds, and it was assayed as to its lytic activity against [3H]thymidine-labeled L929 cells. Dose-response studies revealed that lipid X induced the production of smaller amounts of the tumor-cytotoxic factor than LPS at low concentrations, but it induced that of considerable amounts at and over 1 microgram/ml. Elimination of 1-phosphate or 3-O-beta-hydroxymyristoyl group from lipid X completely prevented the induction of producing this factor by the macrophages. Therefore, it is suggested that both 1-phosphate and 3-O-beta-hydroxymyristoyl groups are essential for the biologic activity of lipid X, as to the induction of the tumor-cytotoxic factor production in the macrophages.
Amano
F
F
Nishijima
M
M
Akamatsu
Y
Y
D000818:Animals; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D006017:Glycolipids / Q000276:immunology / Q000494:pharmacology*; D006023:Glycoproteins / Q000096:biosynthesis*; D008050:Lipid A / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D009005:Monosaccharides / Q000494:pharmacology; D009374:Neoplasms, Experimental / Q000276:immunology / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha
D006017:Glycolipids; D006023:Glycoproteins; D008050:Lipid A; D008070:Lipopolysaccharides; D009005:Monosaccharides; D014409:Tumor Necrosis Factor-alpha; C044283:lipid X