Platelet, but not endothelial, P-selectin is critical for neutrophil-mediated acute postischemic renal failure

In a neutrophil-dependent model of acute postischemic renal failure (APRF), eliminating or blocking P-selectin reduces postischemic neutrophil infiltr ation and preserves kidney function. This study was designed to identify th e role of platelet vs. endothelial P-selectin in APRF. Using wild-type (wt) and P-selectin- deficient (P-/-) mice, we generated chimeric mice by bone marrow transplantation. Chimeric mice exclusively expressed either platelet (Plt-P) or endothelial P-selectin (EC-P). APRF was induced by bilateral re nal ischemia in situ (32 min), followed by reperfusion; 48 h after reperfus ion, EC-P had significantly lower creatinine concentrations (twofold over s ham) than Plt-P (eightfold over sham). Compared with wt, protection from re nal failure in EC-P was similar to that observed in P-/-. Plt-P and EC-P de monstrated similar overall postischemic neutrophil infiltration as measured by renal myeloperoxidase activity. However, Plt-P showed massive neutrophi l infiltration into outer and inner medulla, similar to that in wt. EC-P ha d only patchy, more diffuse neutrophil influx. Our study identifies platele t P-selectin as crucial for postischemic neutrophil recruitment into outer and inner medulla, which is detrimental to the development of APRF. This su ggests that novel therapeutic strategies for postischemic organ failure cou ld be aimed at neutrophil-platelet interactions.