Reduction of severe ischemia/reperfusion injury in rat kidney grafts by a soluble P-selectin glycoprotein ligand

Background. Inflammatory leukocyte-endothelium interactions, mediated by se lectins, contribute to renal ischemia/reperfusion WR) injury. We examined t he influence of the soluble P-selectin glycoprotein ligand I (sPSGL) on ear ly IIR-induced changes in a rat kidney transplantation model with long cold ischemia. Methods. After 24 hr of cold storage, syngeneic kidneys were grafted into b ilaterally nephrectomized rats. Before transplantation, recipients received either 1 mg/kg of sPSGL or vehicle (n=8 per group). Six hours after reperf usion, grafts were removed for light microscopy and immunohistochemistry. C apillary blood flow was measured under a fluorescence microscope by using t he concentric-circles method. Results. A greater proportion, 74.7 +/-7.2% (sPSGL) vs. 28 +/-7.4% (control s), of all dye-labeled outer medullary capillaries appeared in the 12-mum r adius (P <0.01), indicating dense blood flow, whereas 7.6 +/-2.9% vs. 43.3 +/-9.7%, respectively, appeared in the 60-mum radius (P <0.05), indicating rarefied blood flow. In the sPSGL-treated group, the extent of severe tubul ar damage within the inner stripe of the outer medulla was lower compared w ith controls (37.5 +/-8.3% vs. 78.4 +/-3.5%, P <0.01). Outer medullary heat shock protein 72 expression was 14.5 +/-1.6% in the sPSGL-treated group co mpared with 9.6 +/-1.4% in controls (P <0.05). The number of infiltrating p olymorphonuclear leukocytes was similar in both groups. Treatment with sPSG L had no influence on the serum creatinine level. Conclusions. Our data suggest that impairment of outer medullary blood flow is crucial in I/R injury of kidney grafts with prolonged cold storage. Red uction of capillary blood flow perturbations by sPSGL protects tubular cell s from severe structural damage. Blocking early selectin-mediated leukocyte adhesion may have therapeutic implications in improving the prognosis of r enal transplants with severe I/R injury.