Smith S M, Snyder I S
Infect Immun. 1975 Nov;12(5):993-8. doi: 10.1128/iai.12.5.993-998.1975.
Several investigators have reported lipid A as the biologically active unit in the lipopolysaccharide (LPS) molecule. To determine if lipid A was responsible for the reported increases in pyruvate kinase, mice were injected with endotoxin from Salmonella typhimurium SR-11, the Re mutant of Salmonella minnesota R 595, and lipid A-bovine serum albumin conjugate. The livers were homogenized and the activity of pyruvate kinase was measured. Similar increases in enzyme were obtained with all three preparations. These data imply that the lipid portion of the LPS molecule was responsible for alterations in host enzyme activity. To further determine if the lipid portion was the active unit, a lipid-degraded endotoxin (endotoxoid) prepared by potassium methylate treatment was inoculated into mice. An initial increase in liver pyruvate kinase activity was observed with all preparations. The marked increase observed at 16 h with the native product and lipid A conjugate was not obtained with the endotoxoid. These experiments extend and confirm previous observations that lipid A is responsible for the effects associated with LPS. Animals tolerant to endotoxin from S. typhimurium SR-11 were challenged with endotoxin from the Re mutant. A significant increase in pyruvate kinase activity was not obtained, suggesting that anti-O antibodies are not important in the development of tolerance.
几位研究者报道脂多糖（LPS）分子中的脂质A是生物活性单位。为了确定脂质A是否是所报道的丙酮酸激酶增加的原因，给小鼠注射了鼠伤寒沙门氏菌SR-11（明尼苏达沙门氏菌R 595的Re突变体）的内毒素以及脂质A-牛血清白蛋白偶联物。将肝脏匀浆并测定丙酮酸激酶的活性。用这三种制剂均获得了相似的酶活性增加。这些数据表明LPS分子的脂质部分是宿主酶活性改变的原因。为了进一步确定脂质部分是否是活性单位，将通过甲基酸钾处理制备的脂质降解内毒素（类毒素）接种到小鼠体内。所有制剂均观察到肝脏丙酮酸激酶活性最初增加。类毒素未出现天然产物和脂质A偶联物在16小时时观察到的显著增加。这些实验扩展并证实了先前的观察结果，即脂质A是与LPS相关效应的原因。用Re突变体的内毒素攻击对鼠伤寒沙门氏菌SR-11内毒素耐受的动物。未获得丙酮酸激酶活性的显著增加，这表明抗O抗体在耐受性发展中并不重要。
