L-selectin and chemokine response after liver ischemia and reperfusion

L-selectin and chemokine response after liver ischemia and reperfusion
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DOI:
10.1006/jsre.2000.5954
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发表时间:
2000-09-01
影响因子:
2.2
通讯作者:
Ward, PA
Ward, PA
中科院分区:
医学3区
文献类型:
--
作者:
Martinez-Mier, G;Toledo-Pereyra, LH;Ward, PA

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背景:L-选择素在肝脏缺血再灌注(I/R)后肝微血管中PMN的早期募集中起重要作用。在I/R损伤中,白细胞细胞因子趋化因子可引起中性粒细胞(PMN)的激活。在这项研究中,我检测了L-选择素在热缺血90分钟后肝和肺的炎症反应中趋化因子的产生中的作用,研究设计。36只C57BL/6小鼠造成部分肝缺血90min。实验分为3组(每组12只):假手术组、缺血组和L-选择素单抗缺血组。我们在3h进行评估:肝损伤检测,血清趋化因子(MIP-2和MIP-1α),肝和肺组织髓过氧化物酶(MPO),以及肝和肺组织学。统计分析包括单因素方差检验、学生-纽曼-Keuls检验和Kruskal-Wallis多重比较Z值检验。与缺血对照组相比,经L-选择素抗体治疗的缺血组大鼠肝酶水平显著降低,血清MIP-2水平显著降低(P<0.05)。血清MIP-1α水平未见下降,但肝脏和肺组织的中性粒细胞浸润明显改善,反映为MPO水平降低(P&lt;0.05)。与缺血对照组相比,抗L-选择素治疗组大鼠肝脏和肺的组织病理学特征明显改善。我们的研究提示L-选择素在肝脏I/R的发病机制和趋化因子的产生中起重要作用。抗L-选择素治疗可改善肝功能,减少中性粒细胞浸润,降低MIP-2趋化因子反应。(C)2000年学术出版社。
Background L-selectin plays an important role in the early phase of PMNs recruitment in the hepatic microvasculature following liver ischemia and reperfusion (I/R). Leukocyte cytokine chemoattractants (chemokines) cause polymorphonuclear neutrophil (PMN) activation in I/R injury. In this study, me examined the role of L-selectin in the production of chemokines in the Liver and lung inflammatory response following 90 min of warm ischemia,Study design. Thirty-six C57BL/6 mice were subjected to partial liver ischemia for a period of 90 min. Three groups of animals were included (n = 12 per group)-sham group, ischemic control, and the ischemic group receiving monoclonal antibody against L-selectin. We evaluated at 3 h: liver injury measurements, serum chemokines (MIP-2 and MIP-1 alpha), liver and lung tissue myeloperoxidase (MPO), and liver and lung histology. statistical analysis included ANOVA, Student-Newman-Keuls', and Kruskal-Wallis multiple comparison Z-value tests.Results. The ischemic group treated with anti-L-selectin showed significant decreases in liver enzyme levels and a marked decrease in serum MIP-2 (P < 0.05) when compared to ischemic controls. No reduction in serum MIP-1 alpha was noted; however, neutrophil infiltration was significantly ameliorated in the liver and in the lung, as reflected by decreased MPO levels (P < 0.05). Improved histopathological features were observed in the anti-L-selectin-treated group compared to ischemic controls in the Liver and the lung.Conclusions. Our study suggests an important role for L-selectin in the pathogenesis of Liver I/R and the production of chemokines. Anti-L-selectin treatment resulted in improved liver function, decreased neutrophil infiltration, and decreased MIP-2 chemokine response. (C) 2000 Academic Press.