ACUTE PASSIVE ANTIGLOMERULAR BASEMENT-MEMBRANE NEPHRITIS IN P-SELECTIN-DEFICIENT MICE

P-selectin present on surfaces of activated endothelium and platelets mediates neutrophil-endothelial and neutrophil-platelet interactions. The role of P-selectin in vivo was examined in a model of acute passiv e anti-GEM nephritis in P-selectin-deficient and wild-type mice which was induced by intravenous injection of anti-GEM serum. There were two major differences between P-selectin-deficient and wild-type mice. Fi rstly, mutant mice had approximately two fold more glomerular PMNs and albuminuria than wild-type animals at the peak of neutrophil influx a nd proteinuria. Secondly, Lipoxin A(4) (LXA(4)), an eicosanoid which i nhibits leukocyte-endothelial adhesion in vitro, and is generated prim arily by transcellular biosynthetic routes during P-selectin-mediated platelet-PMN interaction [1], was approximately 60% of wild type level s in nephritic kidneys of P-selectin-deficient mice. Injection of wild -type platelets into P-selectin-null mice restored LXA(4) to wild-type levels. The corresponding PMN influx approximated PMN levels in wild- type mice receiving platelets but urine albuminuria remained higher. A lthough these two P-selectin-dependent events cannot be directly linke d, our results point to the importance of considering both platelet an d endothelial P-selectin in determining the cellular events in inflamm ation.