Leukocyte transmigration in inflamed liver: A role for endothelial cell-selective adhesion molecule
Leukocyte transmigration in inflamed liver: A role for endothelial cell-selective adhesion molecule
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DOI：
10.1016/j.jhep.2008.11.027
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发表时间：
2009-04-01
影响因子：
25.7
通讯作者：
Krombach, Fritz
中科院分区：
文献类型：
--
作者：
Khandoga, Andrej;Huettinger, Stefanie;Krombach, Fritz
背景/目的：本研究旨在探讨内皮细胞选择性粘附分子（ESAM），一个最近发现的受体表达在内皮细胞紧密连接和血小板，白细胞迁移在炎症liver.Methods的作用：ESAM的白细胞迁移在肝脏中的作用进行了分析使用ESAM缺陷小鼠在热肝缺血再灌注模型（90分钟/30-360分钟）。在组织切片中定量移出的白细胞。ESAM-/-小鼠在再灌注2 h后，血后中性粒细胞迁移显著减弱，而在6 h后完全恢复。相比之下，ESAM+/+和ESAM-/-小鼠之间的T细胞迁移没有差异。使用活体显微镜，我们证明，ESAM缺乏减弱I/R诱导的血管渗漏后30分钟的再灌注。I/R诱导的升高AST/ALT活性，窦灌注失败，和TUNEL阳性肝细胞的数量之间ESAM+/+和ESAM-/- mice.Conclusions：ESAM是在postischemic肝和介导的中性粒细胞，但不是T细胞在早期再灌注迁移。ESAM缺陷减弱I/R诱导的血管渗漏，不影响白细胞粘附。尽管对中性粒细胞迁移有影响，但ESAM缺乏并不能保护I/R诱导的损伤。(c)2009年欧洲肝脏研究协会。Elsevier B. V.出版，保留所有权利。
Background/Aims:This study was designed to investigate the role of endothelial cell-selective adhesion molecule (ESAM), a recently discovered receptor expressed in endothelial tight junctions and platelets, for leukocyte migration in inflamed liver.Methods:The role of ESAM for leukocyte migration in the liver was analyzed using ESAM-deficient mice in a model of warm hepatic ischemia-reperfusion (90 min/30-360 min).Results: As shown by immunostaining, ESAM is expressed in sinusoids as well as in venules and is not upregulated upon I/R. Emigrated leukocytes were quantified in tissue sections. Postischermic neutrophil transmigration was significantly attenuated in ESAM-/- mice after 2 h of reperfusion, whereas it was completely restored after 6 h. In contrast, T-cell migration did not differ between ESAM+/+ and ESAM-/- mice. Using intravital microscopy, we demonstrate that ESAM deficiency attenuates I/R-induced vascular leakage after 30 min of reperfusion. The I/R-induced elevation in AST/ALT activity, the sinusoidal perfusion failure, and the number of TUNEL-positive hepatocytes were comparable between ESAM+/+ and ESAM-/- mice.Conclusions: ESAM is expressed in the postischemic liver and mediates neutrophil but not T-cell transmigration during early reperfusion. ESAM deficiency attenuates I/R-induced vascular leakage and does not affect leukocyte adherence. Despite the effect on neutrophil migration, ESAM-deficiency does not protect from I/R-induced injury. (c) 2009 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.