Ischemia-reperfusion injury is attenuated in VAP-1-deficient mice and by VAP-1 inhibitors

Jan Kiss, Sirpa Jalkanen, Ferenc Fülöp, Timo Savunen, Marko Salmi

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Neutrophils mediate the damage caused by ischemia-reperfusion both at the site of primary injury and in remote organs. Vascular adhesion protein-1 (VAP-1) is an ectoenzyme expressed on endothelial cells and it has been shown to regulate leukocyte extravasation. Here we show for the first time using VAP-1-deficient mice that VAP-1 plays a significant role in the intestinal damage and acute lung injury after ischemia-reperfusion. Separate inhibition of VAP-1 by small molecule enzyme inhibitors and a function-blocking monoclonal antibody in WT mice revealed that the catalytic activity of VAP-1 is responsible for its pro-inflammatory action. The use of transgenic humanized VAP-1 mice also showed that the enzyme inhibitors alleviate both the ischemia-reperfusion injury in the gut and neutrophil accumulation in the lungs. These data thus indicate that VAP-1 regulates the inflammatory response in ischemia-reperfusion injury and suggest that blockade of VAP-1 may have therapeutic value.

Original languageEnglish
Pages (from-to)3041-3049
Number of pages9
JournalEuropean journal of immunology
Volume38
Issue number11
DOIs
Publication statusPublished - Dec 1 2008

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Keywords

  • Adhesion molecules
  • Inflammation
  • Ischemia-reperfusion injury

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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