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

Alaa S. Awad, Michael Rouse, Liping Huang, Amy L. Vergis, Jörg Reutershan, Helen P. Cathro, Joel Linden, Mark D. Okusa

Research output: Contribution to journalArticlepeer-review

136 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)689-698
Number of pages10
JournalKidney international
Volume75
Issue number7
DOIs
StatePublished - Apr 2009

Keywords

  • A-agonists
  • Acute lung injury
  • Flow cytometry
  • Ischemia/reperfusion
  • Neutrophil migration

ASJC Scopus subject areas

  • Nephrology

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