Cytotoxicity of the glycolipid region of streptococcal lipoteichoic acid for cultures of human heart cells.
The ability of LTA of Streptococcus pyogenes to stimulate cell division or to kill tissue culture cells derived from human heart was investigated. Initial studies indicated that at low concentrations, ranging from 0.01 to 1.0 micrograms/ml, LTA stimulated cell division, whereas at higher concentrations, ranging from 10 to 1000 micrograms/ml, it killed the cells. Deacylated lipoteichoic acid, which lacked cell membrane binding activity, similarly stimulated or killed the heart cells depending on the concentration added to the tissue cultures. Fractionation of LTA after mild ammonia hydrolysis yielded a polyglycerophosphate and polar lipid fraction, both of which retained the glucose from the glycolipid moiety of the LTA molecule, and a neutral lipid fraction that was devoid of phosphorus or glucose. Toxic activity was present only in the fractions containing glucose. Oxidation of LTA or its deacylated derivative with sodium metaperiodate reduced the assayable glucose content without destroying the polyglycerophosphate backbone and resulted in a parallel loss of cytotoxicity, strongly suggesting that the glucose moieties of S. pyogenes LTA must be intact for the toxic activity against human heart cells to be expressed.
D000215:Acylation; D002478:Cells, Cultured; D004187:Disaccharides / Q000633:toxicity; D006017:Glycolipids / Q000633:toxicity*; D006801:Humans; D006868:Hydrolysis; D008055:Lipids / Q000172:deficiency / Q000633:toxicity; D008070:Lipopolysaccharides; D009206:Myocardium / Q000166:cytology*; D010504:Periodic Acid / Q000494:pharmacology; D010712:Phosphatidic Acids / Q000378:metabolism / Q000633:toxicity*; D013297:Streptococcus pyogenes / Q000378:metabolism; D013682:Teichoic Acids / Q000378:metabolism / Q000633:toxicity*; D013936:Thymidine / Q000378:metabolism
D004187:Disaccharides; D006017:Glycolipids; D008055:Lipids; D008070:Lipopolysaccharides; D010712:Phosphatidic Acids; D013682:Teichoic Acids; D010504:Periodic Acid; C009900:lipoteichoic acid; C009288:metaperiodate; D013936:Thymidine