Potent leukocidal action of Escherichia coli hemolysin mediated by permeabilization of target cell membranes.
Potent leukocidal action of Escherichia coli hemolysin mediated by permeabilization of target cell membranes.
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靶细胞膜通透性介导的大肠杆菌血素蛋白的有效白细胞囊性作用。
DOI：
10.1084/jem.169.3.737
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发表时间：
1989-03-01
影响因子：
15.3
通讯作者：
Hugo, F
中科院分区：
文献类型：
--
作者：
Bhakdi, S;Greulich, S;Muhly, M;Eberspacher, B;Becker, H;Thiele, A;Hugo, F
大肠杆菌溶血素(ECH)对细菌毒力的贡献主要与其溶血特性有关。我们在此报告，这种流行的细菌溶血素是迄今已知的最有效的杀白素。极低浓度(约1 ng/ml)的ECH可引起PMN膜通透性缺陷(2-10×10(6)cell/ml)，导致细胞内三磷酸腺苷外流和碘化丙啶内流。被攻击的细胞似乎不能修复膜损伤。人血清白蛋白、高密度和低密度脂蛋白以及免疫球蛋白共同保护红细胞和血小板免受高剂量(5-25微克/毫升)ECH的攻击。相反，在这些血浆灭活剂存在的情况下，ECH在低剂量(50-250 ng/ml)下仍可使PMN通透。因此，PMN成为ECH在人体血液和富含蛋白质的体液中攻击的首选靶点。动力学研究表明，膜通透性是一个快速的过程，在毒素作用于白细胞后几秒钟内就开始释放ATP。据估计，大约300个ECH/PMN分子结合后，膜就会发生通透性。这个过程与颗粒胞吐和细胞吞噬杀伤能力的丧失是平行的。ECH通过在生理条件下攻击粒细胞直接中和人体的一个主要免疫防御机制，这一认识为它作为大肠杆菌毒力因子的可能作用和潜在重要性提供了新的线索。
The contribution of Escherichia coli hemolysin (ECH) to bacterial virulence has been considered mainly in context with its hemolytic properties. We here report that this prevalent bacterial cytolysin is the most potent leukocidin known to date. Very low concentrations (approximately 1 ng/ml) of ECH evoke membrane permeability defects in PMN (2-10 x 10(6) cells/ml) leading to an efflux of cellular ATP and influx of propidium iodide. The attacked cells do not appear to repair the membrane lesions. Human serum albumin, high density and low density lipoprotein, and IgG together protect erythrocytes and platelets against attack by even high doses (5-25 micrograms/ml) of ECH. In contrast, PMN are still permeabilized by ECH at low doses (50-250 ng/ml) in the presence of these plasma inactivators. Thus, PMN become preferred targets for attack by ECH in human blood and protein-rich body fluids. Kinetic studies demonstrate that membrane permeabilization is a rapid process, ATP-release commencing within seconds after application of toxin to leukocytes. It is estimated that membrane permeabilization ensues upon binding of approximately 300 molecules ECH/PMN. This process is paralleled by granule exocytosis, and by loss of phagocytic killing capacity of the cells. The recognition that ECH directly counteracts a major immune defence mechanism of the human organism through its attack on granulocytes under physiological conditions sheds new light on its possible role and potential importance as a virulence factor of E. coli.