Apoptotic cell administration is detrimental in murine renal ischaemia reperfusion injuryReport as inadecuate




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Journal of Inflammation

, 11:31

First Online: 10 October 2014Received: 07 April 2014Accepted: 01 October 2014

Abstract

BackgroundAcute kidney injury induced by renal ischaemia reperfusion injury IRI is characterised by renal failure, acute tubular necrosis ATN, inflammation and microvascular congestion. The administration of apoptotic cells ACs has been shown to reduce inflammation in various organs including the liver and kidney. This study explored whether AC administration prior to the induction of renal IRI was protective.

FindingsRenal IRI was induced in Balb-c mice by clamping the renal blood vessels for either 20, 24 or 25 minutes to induce mild, moderate or severe kidney dysfunction respectively. Renal function and injury was determined 24 hours following IRI by measurement of plasma creatinine and ATN scoring respectively. ACs were generated from Balb-c thymocytes and classified as either predominantly early or late apoptotic by Annexin-V and propidium iodide staining. Early AC administration prior to severe IRI had no influence on plasma creatinine or ATN severity. In contrast, administration of early or late ACs significantly worsened renal function in mice with mild or moderate renal IRI, respectively, compared to PBS treated controls, though ATN scores were comparable. Despite ACs exerting pro-coagulant effects, the worsening of renal function was not secondary to increased microvascular congestion, inferred by fibrin and platelet CD41 deposition, or inflammation, assessed by neutrophil infiltration.

ConclusionsDespite the AC-derived protection demonstrated in other organs, ACs do not protect mice from renal IRI. ACs may in fact further impair renal function depending on injury severity. These data suggest that AC-derived protection is not translationally relevant for patients with acute kidney injury induced by ischaemic injury.

KeywordsIschaemia reperfusion injury Acute kidney injury Apoptotic cells Inflammation Microvasculature AbbreviationsACsApoptotic cells

AKIAcute kidney injury

ATNAcute tubular necrosis

CIACollagen induced arthritis

IFImmunofluorescence

IHCImmunohistochemistry

ILInterleukin

IRIIschaemia reperfusion injury

LPSLipopolysaccharide

OSOMOuter stripe of the outer medulla

PIPropidium iodide

PSPhosphatidylserine

TGF-αTransforming growth factor-α

TNF-βTumour necrosis factor-β

Electronic supplementary materialThe online version of this article doi:10.1186-s12950-014-0031-6 contains supplementary material, which is available to authorized users.

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Author: Emily E Hesketh - David C Kluth - Jeremy Hughes

Source: https://link.springer.com/







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