Dubor F, Dosne A M, Chedid L A
Infect Immun. 1986 Jun;52(3):725-9. doi: 10.1128/iai.52.3.725-729.1986.
The effect of lipopolysaccharide (LPS) on the production of fibrinolytic inhibitor by human endothelial cells was determined because results of previous experiments have shown us that it is possible to stimulate this synthesis with muramyl dipeptide. Treatment of these cells with LPS resulted in a marked enhancement of fibrinolytic inhibitor, as estimated in a urokinase-induced fibrinolysis assay. A dose-response curve was obtained for LPS concentrations ranging from 10 to 1,000 ng/ml, thus demonstrating the great sensitivity of these cells. This inhibitor did not reduce plasmin activity and formed complexes with high- and low-molecular-weight urokinase as visualized by fibrin enzymography on sodium dodecyl sulfate-polyacrylamide electrophoretic gels. The molecular weight of this inhibitor was estimated to be 54 to 58 kilodaltons. These findings led us to conclude that LPS stimulates formation of a plasminogen antiactivator. This LPS effect could be suppressed by polymyxin B and colimycin. The stimulatory effect of muramyl dipeptide required doses which were at least 1,000 times greater than those of LPS and was not decreased by polymyxin B. These results show the possibility of independent modulation of plasminogen antiactivator production at the endothelial level, which could be important in endotoxemia. Under these conditions colimycin might have an additional advantage for clinical use because of its ability to prevent fibrinolytic inhibition.
由于先前实验结果表明用胞壁酰二肽刺激这种合成是可能的，因此测定了脂多糖（LPS）对人内皮细胞纤溶抑制剂产生的影响。在用尿激酶诱导的纤溶测定法中估计，用LPS处理这些细胞导致纤溶抑制剂显著增强。获得了LPS浓度范围为10至1000 ng/ml的剂量反应曲线，从而证明了这些细胞的高敏感性。这种抑制剂不会降低纤溶酶活性，并且在十二烷基硫酸钠-聚丙烯酰胺电泳凝胶上通过纤维蛋白酶谱法可见，它与高分子量和低分子量尿激酶形成复合物。这种抑制剂的分子量估计为54至58千道尔顿。这些发现使我们得出结论，LPS刺激纤溶酶原抗激活剂的形成。这种LPS效应可被多粘菌素B和黏菌素抑制。胞壁酰二肽的刺激作用所需剂量至少比LPS大1000倍，并且不会被多粘菌素B降低。这些结果表明在内皮水平上独立调节纤溶酶原抗激活剂产生的可能性，这在内毒素血症中可能很重要。在这些情况下，黏菌素由于其预防纤溶抑制的能力，可能在临床应用中具有额外的优势。
