Structural and physicochemical requirements of endotoxins for the activation of arachidonic acid metabolism in mouse peritoneal macrophages in vitro.
Structural and physicochemical requirements of endotoxins for the activation of arachidonic acid metabolism in mouse peritoneal macrophages in vitro.
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体外激活小鼠腹腔巨噬细胞花生四烯酸代谢的内毒素的结构和理化要求。
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发表时间：
1989
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通讯作者：
E. Rietschel
中科院分区：
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作者：
T. Lüderitz;K. Brandenburg;U. Seydel;A. Roth;C. Galanos;E. Rietschel
研究了不同野生型和突变革兰氏阴性细菌的脂多糖以及合成的和无菌脂质A在体外激活小鼠腹腔巨噬细胞花生四烯酸代谢的能力。结果发现，沙门氏菌和大肠杆菌（Re至Rc化学型）的深粗糙突变体的脂多糖刺激巨噬细胞释放大量的白三烯C4（LTC 4）和前列腺素E2（PGE 2）。野生型菌株（S. abortus equi、马流产沙门氏菌S. friedenau）仅诱导PGE 2而不诱导LTC 4形成。出乎意料的是，游离细菌和合成的E. coli lipid A对LTC 4和PGE 2的诱导作用较弱。脱酰Re突变体脂多糖制剂无活性。然而，巨噬细胞与脱酰脂多糖和脂质A的共孵育导致显著量的LTC 4和PGE 2的释放，类似于用Re-mutant脂多糖获得的那些。脂多糖的脂质A部分对于诱导LTC 4的重要性通过证明内毒素低应答小鼠或对内毒素耐受的小鼠的腹腔巨噬细胞在用Re-突变体脂多糖刺激时不对花生四烯酸代谢物的释放作出应答并且多粘菌素B阻止Re-脂多糖诱导的LTC 4和PGE 2释放来指示。物理测量表明，游离脂质A和S-型脂多糖的相变温度均高于37摄氏度，而R-突变体脂多糖的相变温度则明显较低（30-35摄氏度）。因此，与调查的材料，相变温度和引发LTC 4生产的能力之间的反比关系被揭示。
Lipopolysaccharides of different wild-type and mutant gram-negative bacteria, as well as synthetic and bacterial free lipid A, were studied for their ability to activate arachidonic acid metabolism in mouse peritoneal macrophages in vitro. It was found that lipopolysaccharides of deep-rough mutants of Salmonella minnesota and Escherichia coli (Re to Rc chemotypes) stimulated macrophages to release significant amounts of leukotriene C4 (LTC4) and prostaglandin E2 (PGE2). Lipopolysaccharides of wild-type strains (S. abortus equi, S. friedenau) only induced PGE2 and not LTC4 formation. Unexpectedly, free bacterial and synthetic E. coli lipid A were only weak inducers of LTC4 and PGE2 production. Deacylated Re-mutant lipopolysaccharide preparations were inactive. However, co-incubation of macrophages with both deacylated lipopolysaccharide and lipid A lead to the release of significant amounts of LTC4 and PGE2, similar to those obtained with Re-mutant lipopolysaccharide. The significance of the lipid A portion of lipopolysaccharide for the induction of LTC4 was indicated by demonstrating that peritoneal macrophages of endotoxin-low-responder mice or of mice rendered tolerant to endotoxin did not respond with the release of arachidonic acid metabolites on stimulation with Re-mutant lipopolysaccharide and that polymyxin B prevented the Re-lipopolysaccharide-induced LTC4 and PGE2 release. Physical measurements showed that the phase-transition temperatures of both free lipid A and S-form lipopolysaccharide were above 37 degrees C while those of R-mutant lipopolysaccharides were significantly lower (30-35 degrees C). Thus, with the materials investigated, an inverse relationship between the phase-transition temperature and the capacity to elicit LTC4 production was revealed.