ROLE OF SELECTINS IN LOCAL AND REMOTE TISSUE-INJURY FOLLOWING ISCHEMIA AND REPERFUSION

Ischemia (4-hour) followed by reperfusion (4-hour) of rat hind limbs r esults in local injury as well as remote (lung) injury. It has recentl y been shown that injury in this model is neutrophil- and cytokine-dep endent 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 eithe r through the use of blocking antibodies to L-, E- or P-selectins or b y the use of oligosaccharides that are reactive with selectins. Lung i njury was found to be L- and E-selectin-dependent. When the ischemia a nd reperfusion times were reduced, lung injury was also found to be P- selectin dependent. In the case of hind limb injury involving the crur al muscle mass, injury was L-selectin-dependent but independent of req uirements for P- and E-selectin. Injury in both organs was blocked by the infusion of sialylated Lewis(x) pentasaccharide, whereas sialyl-N- acetyllactosamine pentasaccharide failed to protect against injury. In general, when selectin-blocking approaches were protective, there wer e parallel reductions in tissue content of myeloperoxidase. These data underscore the role of selectins In ischemia-reperfusion injury and s uggest that selectin requirements may vary with the vascular bed under study.