Adhesion Molecules Involved in Neutrophil Recruitment during Sepsis-Induced Acute Kidney Injury
Adhesion Molecules Involved in Neutrophil Recruitment during Sepsis-Induced Acute Kidney Injury
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DOI：
10.1159/000358238
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发表时间：
2014-01-01
影响因子：
5.3
通讯作者：
Zarbock, Alexander
中科院分区：
文献类型：
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作者：
Herter, Jan M.;Rossaint, Jan;Zarbock, Alexander
急性肾损伤（阿基）是危重患者的常见并发症，与高死亡率相关。中性粒细胞的募集是阿基发病机制的标志。虽然缺血再灌注损伤（IRI）是阿基的常用研究模型，但IRI诱导的阿基的临床相关性有限。在流行病学上，脓毒症是肾损伤的主要原因。然而，这些不同的阿基实体是否具有相同的病理生理学机制仍然是未知的。本研究旨在研究脓毒症诱导的阿基小鼠模型中中性粒细胞募集到肾脏中的分子机制。通过使用基于流式细胞术的方法，我们表明两种β 2-整合素Mac-1和莱亚-1以及E-选择素和P-选择素参与诱导脓毒症后中性粒细胞向肾脏的募集。使用活体显微镜进一步研究了中性粒细胞募集的分子机制，表明阻断这四种分子之一可减少粘附白细胞的数量。这伴随着脓毒症诱导后E-选择素、P-选择素和ICAM-1（内皮细胞上β（2）-整合素的反受体）的肾上调。我们得出的结论是，阻断P-选择素、E-选择素、Mac-1或莱亚-1可以保护小鼠免受败血症诱导的阿基。(C)2014 S. Karger AG，巴塞尔
Acute kidney injury (AKI) is a common complication in critically ill patients and is associated with high mortality. Recruitment of neutrophils is a hallmark in the pathogenesis of AKI. Although ischemia-reperfusion injury (IRI) is a frequently used research model of AKI, the clinical relevance of IRI-induced AKI is limited. Epidemiologically, sepsis is the prevailing cause of kidney injury. However, it is still unknown whether these distinct entities of AKI share the same pathophysiological mechanisms. This study was initiated to investigate the molecular mechanisms of neutrophil recruitment into the kidney in a murine model of sepsis-induced AKI. By using a flow cytometry-based method, we show that the two beta(2)-integrins Mac-1 and LEA-1 as well as E-selectin and P-selectin are involved in neutrophil recruitment into the kidney after induction of sepsis. The molecular mechanisms of neutrophil recruitment were further investigated using intravital microscopy, demonstrating that blocking one of these four molecules reduces the number of adherent leukocytes. This was accompanied by a renal upregulation of E-selectin, P-selectin and ICAM-1 (the counter-receptor of beta(2)-integrins on endothelial cells) after sepsis induction. We conclude that blocking P-selectin, E-selectin, Mac-1 or LEA-1 protects mice from sepsis-induced AKI. (C) 2014 S. Karger AG, Basel