Uptake and deacylation of bacterial lipopolysaccharides by macrophages from normal and endotoxin-hyporesponsive mice.
Macrophages are thought to play a central role in the responses of animals to gram-negative bacterial lipopolysaccharides (LPS). Since nothing is known about the metabolism of LPS by these cells, we studied the uptake and deacylation of radiolabeled LPS by thioglycolate-elicited peritoneal macrophages from normal (C3H/HeN) and LPS-hyporesponsive (C3H/HeJ) mice. Macrophages from both kinds of mice took up and deacylated LPS that were added to the culture medium. Opsonization of the LPS with anti-LPS immunoglobulin G antibodies greatly increased LPS uptake; the opsonized LPS also underwent deacylation at rates that were directly related to the amount of cell-associated LPS. An analysis of the fatty acid composition of the cell-associated LPS indicated that the cells have one or more acyloxyacyl hydrolases that remove the non-hydroxylated fatty acids that are normally substituted to the hydroxyl groups of (glucosamine-linked) 3-hydroxytetradecanoate residues in lipid A; we also found evidence for deacylation of 3-hydroxytetradecanoate from the glucosamine backbone. LPS deacylation by macrophages from C3H/HeN and C3H/HeJ mice was qualitatively and quantitatively similar. Nonopsonized LPS are able to stimulate LPS-responsive cells; in these studies we established that animal cells can deacylate nonopsonized LPS, thus raising the possibility that LPS metabolism may play a role in modulating cellular stimulation.
D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D002452:Cell Count; D015232:Dinoprostone; D005227:Fatty Acids / Q000032:analysis; D007074:Immunoglobulin G / Q000276:immunology; D007700:Kinetics; D008050:Lipid A / Q000032:analysis / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000032:analysis / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D008262:Macrophage Activation; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008809:Mice, Inbred C3H; D009895:Opsonin Proteins; D011458:Prostaglandins E / Q000378:metabolism; D012486:Salmonella typhimurium
D000907:Antibodies, Bacterial; D005227:Fatty Acids; D007074:Immunoglobulin G; D008050:Lipid A; D008070:Lipopolysaccharides; D009895:Opsonin Proteins; D011458:Prostaglandins E; D015232:Dinoprostone