Role of selectins in local and remote tissue injury following ischemia and reperfusion.
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| Abstract |
Ischemia (4-hour) followed by reperfusion (4-hour) of rat hind limbs results in local injury as well as remote (lung) injury. It has recently been shown that injury in this model is neutrophil- and cytokine-dependent and requires the beta 2 integrin adhesion molecules CD11a/CD18 and CD11b/CD18. The role of selectins in events leading to injury (as determined by leakage of albumin and by hemorrhage) was assessed either through the use of blocking antibodies to L-, E- or P-selectins or by the use of oligosaccharides that are reactive with selectins. Lung injury was found to be L- and E-selectin-dependent. When the ischemia and reperfusion times were reduced, lung injury was also found to be P-selectin dependent. In the case of hind limb injury involving the crural muscle mass, injury was L-selectin-dependent but independent of requirements for P- and E-selectin. Injury in both organs was blocked by the infusion of sialylated Lewis pentasaccharide, whereas sialyl-N-acetyllactosamine pentasaccharide failed to protect against injury. In general, when selectin-blocking approaches were protective, there were parallel reductions in tissue content of myeloperoxidase. These data underscore the role of selectins in ischemia-reperfusion injury and suggest that selectin requirements may vary with the vascular bed under study.
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| Authors | A Seekamp, G O Till, M S Mulligan, J C Paulson, D C Anderson, M Miyasaka, P A Ward |
| Journal | The American journal of pathology (Am J Pathol) Vol. 144 Issue 3 Pg. 592-8 (Mar 1994) ISSN: 0002-9440 [Print] United States |
| PMID | 7510457 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.) |
| Chemical References |
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