Independent pathways of P-selectin and complement-mediated renal ischemia/reperfusion injury.
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| Abstract |
Evidence from in vitro studies indicates that complement activation regulates the expression of P-selectin on endothelial cells. This suggests that in disorders such as ischemia/reperfusion injury, in which both complement and P-selectin have been shown to play a role, complement activation is a primary event and the effects of P-selectin are secondary. To test this hypothesis in vivo, we examined a mouse kidney model of ischemia/reperfusion injury. Surprisingly, the time course and extent of expression of P-selectin was unaltered in C3-deficient mice compared with wild-type mice, in which there was rapid but transient up-regulation of P-selectin on capillary walls and slower accumulation of complement split product on the tubular epithelium. In addition, treatment with anti-P-selectin antibody to reduce the neutrophil-mediated reperfusion damage was equally effective in the absence of C3. These data imply that complement and P-selectin-mediated pathways of renal reperfusion injury are mutually independent, a conclusion that is possibly explained by the differences in the location and time kinetics of complement activation and P-selectin expression. We conclude that in vivo interaction between complement and P-selectin is limited because of time and spatial considerations. Consequently, complement and P-selectin pose distinct targets for therapy.
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| Authors | Conrad A Farrar, Yi Wang, Steven H Sacks, Wuding Zhou |
| Journal | The American journal of pathology (Am J Pathol) Vol. 164 Issue 1 Pg. 133-41 (Jan 2004) ISSN: 0002-9440 [Print] United States |
| PMID | 14695327 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't) |
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