期刊
JOURNAL OF INNATE IMMUNITY
卷 6, 期 5, 页码 597-606出版社
KARGER
DOI: 10.1159/000358238
关键词
Neutrophil recruitment; Acute kidney injury; Adhesion molecules; Selectins; Integrins
类别
资金
- German Research Foundation [AZ 428/3-1, AZ 428/6-1, SFB 1009/A5, HE-6810/1-1]
- Interdisciplinary Center of Clinical Research
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
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