Molecular biological study of leukotoxin and its diol-induced cell activation and injury -experimental model of ARDS-

我们先前报道了leutoxin（Lx）、linolate的epoxide，以及激活的pulmonary vascular endothelial nitric oxide合成酶和xanthine oxidase，生产nitric oxide和Oy-D22 dy-D2-负责，可能有害的细胞。我们想知道Lx可以激活中性植物和alveolar macrophage，炎症性噬细胞。我们也很想知道哪一种环氧丙烷-Lx二醇，哪一种Lx-二醇被报道成为一种重要的细胞毒性物质，真正地将其毒性表现在脉冲式脉管内的细胞中。To answer these questions we tested the experiments using human neutrophils （PMN）、rat alveolar macrophage （Mac）、human pulmonary artery endothelial cell （HPAEC）和chinese hamster ovary cell （CHO）。Lx和Lx-diol Caused Potent chemotaxis of PMN通过pertussis toxin-sensitive signal transduction而没有CDIIb或CD 18 adhesion molecules或production of peroxides。Lx，如何，没有激活Mac在硝酸氧化物或O-D22-D2生产条件下-用TNFα的缓慢增强生产，Lx及其二醇导致HPAEC的缓慢损害，当细胞谷氨酸含量被破坏的LX具有更多的细胞毒性。TSO，另一环氧乙烷，也是CHO中的细胞毒性，而TSO诱导的细胞毒性在人体溶解环氧乙烷水解酶（hsEH） cDNA转染CHO中受到关注。由于TSO-diol损伤的glutathione-depleted hsEH cDNA转染的CHO，glutathione-diol-induced损伤是一种基本物质。我们目前的研究建议导致Lx及其二醇的影响，以及进一步的建议glutathione-depleted pathological state，这可能包括ARDS可能增加的细胞毒性的Lx和Lx-diol。

We previously reported that leukotoxin (Lx), an epoxide of linolate, which activated pulmonary vascular endothelial nitric oxide synthase and xanthine oxidase, producing nitric oxide and OィイD22ィエD2-respectively, potentially injured cells. We wondered whether Lx could activate neutrophils and alveolar macrophage, inflammatory phagocytic cells. We also wondered whether epoxide-diol of Lx, a Lx-diol which was reported to be an important cellular toxic substance, realy exert its toxicity in pulmonary vascular endothelial cells. To answer these questions we tested the experiments using human neutrophils (PMN), rat alveolar macrophage (Mac), human pulmonary artery endothelial cell (HPAEC) and chinese hamster ovary cell (CHO). Lx and Lx-diol caused potent chemotaxis of PMN via pertussis toxin-sensitive signal transduction without expression of CDIIb or CD18 adhesion molecules or production of peroxides. Lx, however, did not activate Mac in terms of production of nitric oxide or OィイD22ィエD2- with slight enhanced production of TNFα.Lx and its diol caused slight injury of HPAEC, however, when cell glutathione contents were depleted Lx exerted more potent cytotoxicity. TSO, another epoxide, also exerted cytotoxicity in CHO whereas TSO-induced cytotoxicity was attenuated in human soluble epoxide hydrolase (hsEH) cDNA transfected CHO. Since TSO-diol injured glutathione-depleted hsEH cDNA transfected CHO, glutathione was an essential substance against epoxide-diol-induced injury. Our current study suggests inflammation provoking effects of Lx and its diol and further suggests glutathione-depleted pathological state such an acute lung injury including ARDS may augment cytotoxicity of Lx and Lx-diol.