| First Author | Kiss J | Year | 2008 |
| Journal | Eur J Immunol | Volume | 38 |
| Issue | 11 | Pages | 3041-9 |
| PubMed ID | 18991279 | Mgi Jnum | J:141405 |
| Mgi Id | MGI:3818219 | Doi | 10.1002/eji.200838651 |
| Citation | Kiss J, et al. (2008) Ischemia-reperfusion injury is attenuated in VAP-1-deficient mice and by VAP-1 inhibitors. Eur J Immunol 38(11):3041-9 |
| abstractText | 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. |
