A blockade of complement activation prevents rapid intestinal ischaemia-reperfusion injury by modulating mucosal mast cell degranulation in rats

Clinical and Experimental Immunology
T KimuraT Bamba

Abstract

We attempted to define the putative role of complement activation in association with mucosal mast cell (MMC) degranulation in the pathogenesis of rapid intestinal ischaemia-reperfusion (I/R) injury. We prepared complement activity-depleted rats by the administration of the anti-complement agent K-76COOH and the serine-protease inhibitor FUT-175. Autoperfused segments of the jejunum were exposed to 60 min of ischaemia, followed by reperfusion for various time periods, and the epithelial permeability was assessed by the 51Cr-EDTA clearance rate. The number of MMC was immunohistochemically assessed. In control rats, the maximal increase in mucosal permeability was achieved by 30-45 min of reperfusion. This increase was significantly attenuated by the administration of either K-76COONa alone or in combination with FUT-175. In contrast, the administration of carboxypeptidase inhibitor (CPI), which prevents the inactivation of complement-derived anaphylatoxins such as C5a, significantly enhanced the increase in I/R-induced mucosal permeability. These findings were confirmed morphologically by light microscopy and scanning electron microscopy. In addition, the I/R-induced mucosal injury was accompanied by a marked decrease in the num...Continue Reading

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Citations

Mar 5, 2004·Proceedings of the National Academy of Sciences of the United States of America·Ming ZhangMichael C Carroll
Aug 12, 2014·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·Mu-qing YangJi-yu Li
Jan 19, 2016·Frontiers in Immunology·Melissa Krystel-WhittemoreJohn G Wood
Nov 19, 2015·Microbiology and Immunology·Eszter TubolyHidechika Okada
Jul 28, 2012·European Journal of Medicinal Chemistry·Enrique L LarghiTeodoro S Kaufman
Jun 26, 2012·The Journal of Allergy and Clinical Immunology·Beatrix SchäferStephen J Galli
Feb 22, 2005·Neoplasia : an International Journal for Oncology Research·Karin E de VisserLisa M Coussens
Jan 23, 2016·BioMed Research International·Konstantina KatseniKonstantinos Katsenis
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Aug 27, 2021·Drug Discovery Today·Sherin SaheeraRajarajan A Thandavarayan

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