Tatsumi T, Fliss H
Department of Physiology, Faculty of Medicine, University of Ottawa, Ontario, Canada.
Am J Physiol. 1994 Oct;267(4 Pt 2):H1597-607. doi: 10.1152/ajpheart.1994.267.4.H1597.
The migration of neutrophils through the endothelium at sites of inflammation may be facilitated by oxidant-mediated disruption of cellular junctions. The present study examined the effects of noncytotoxic concentrations of the membrane-penetrating neutrophil oxidants hypochlorous acid (HOCI) and monochloramine (NH2Cl), or the membrane-impermeant taurine chloramine (taurine NCl), on cultured bovine aorta endothelial monolayers. HOCl (25 microM) or NH2Cl (10 microM), but not taurine NCl (100 microM), caused a reversible shortening of the cytoskeletal actin microfilaments, cell retraction, and increased permeability within 2 min. These effects were accompanied by an increase in intracellular zinc concentration as well as the oxidation of intracellular glutathione and protein sulfhydryls. The zinc ionophore pyrithione also increased permeability. HOCl or NH2Cl, but not taurine NCl, also rapidly increased microvascular permeability in isolated perfused rat lungs. The data suggest that HOCl and NH2Cl can increase endothelial permeability by causing very rapid cytoskeletal shortening and cell retraction, possibly as a result of the oxidation of intracellular sulfhydryls and mobilization of zinc.
在炎症部位，氧化剂介导的细胞连接破坏可能会促进中性粒细胞穿过内皮细胞的迁移。本研究检测了非细胞毒性浓度的可穿透细胞膜的中性粒细胞氧化剂次氯酸（HOCI）和一氯胺（NH2Cl），或不可穿透细胞膜的牛磺酸氯胺（牛磺酸NCl）对培养的牛主动脉内皮单层细胞的影响。次氯酸（25微摩尔）或一氯胺（10微摩尔），而非牛磺酸NCl（100微摩尔），在2分钟内导致细胞骨架肌动蛋白微丝可逆性缩短、细胞回缩并增加通透性。这些效应伴随着细胞内锌浓度的增加以及细胞内谷胱甘肽和蛋白质巯基的氧化。锌离子载体吡啶硫酮也增加了通透性。次氯酸或一氯胺，而非牛磺酸NCl，也能迅速增加离体灌注大鼠肺的微血管通透性。数据表明，次氯酸和一氯胺可能通过导致细胞骨架快速缩短和细胞回缩来增加内皮通透性，这可能是细胞内巯基氧化和锌动员的结果。
