Compartmentalization of neutrophils in the kidney and lung following acute ischemic kidney injury.

Compartmentalization of neutrophils in the kidney and lung following acute ischemic kidney injury.
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DOI:
10.1038/ki.2008.648
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发表时间:
2009-04
影响因子:
19.6
通讯作者:
Okusa, Mark D.
Okusa, Mark D.
中科院分区:
医学1区
文献类型:
--
作者:
Awad, Alaa S.;Rouse, Michael;Huang, Liping;Vergis, Amy L.;Reutershan, Joerg;Cathro, Helen P.;Linden, Joel;Okusa, Mark D.

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在肾缺血-再灌注期间,局部和远端组织损伤是由中性粒细胞流入受影响的组织引起的。在这里,我们测量了肾缺血再灌注后中性粒细胞在肾和肺中的边集和移行的动力学。双侧肾损伤后24 h,肾脏中性粒细胞含量增加3倍。嗜中性粒细胞主要存在于血管内皮细胞中,少量存在于血管内皮细胞边缘。与边缘中性粒细胞相比,这些间质中性粒细胞的细胞内IFN-γ、IL-4、IL-6和IL-10水平显著较低,IL-4和TNF-α的量有降低的趋势。通过高分辨率显微镜检查证实中性粒细胞定位于肾间质,这些迁移部位与血管通透性增加的区域直接相关。腺苷2A受体的激活显著降低了约一半的肾脏中性粒细胞迁移和约三分之一的血管通透性。单侧肾缺血-再灌注后,未夹闭的肾脏和肺没有积聚间质中性粒细胞,也没有增加血管通透性,尽管肺中中性粒细胞边缘化显著增加。我们的研究结果表明,在肾缺血再灌注后的组织损伤部位,中性粒细胞从血管系统中依次募集和迁移到肾组织中。
During renal ischemia-reperfusion, local and distant tissue injury is caused by an influx of neutrophils into the affected tissues. Here we measured the kinetics of margination and transmigration of neutrophils in vivo in the kidney and lungs following renal ischemia-reperfusion. After bilateral renal injury, kidney neutrophil content increased threefold at 24 h. The neutrophils were found primarily in the interstitium and to a lesser degree marginated to the vascular endothelium. These interstitial neutrophils had significantly lower levels of intracellular IFN-γ, IL-4, IL-6, and IL-10 a tendency for decreased amounts of IL-4 and TNF-α compared to the marginated neutrophils. Localization of the neutrophils to the kidney interstitium was confirmed by high resolution microscopy and these sites of transmigration were directly associated with areas of increased vascular permeability. Activation of the adenosine 2A receptor significantly decreased both kidney neutrophil transmigration by about half and vascular permeability by about a third. After unilateral renal ischemia-reperfusion, the unclipped kidney and lungs did not accumulate interstitial neutrophils or have increased vascular permeability despite a marked increase of neutrophil margination in the lungs. Our findings suggest there is a sequential recruitment and transmigration of neutrophils from the vasculature into the kidney interstitium at the site of tissue injury following renal ischemia-reperfusion.
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