THE CYTOKINE-ADHESION MOLECULE CASCADE IN ISCHEMIA REPERFUSION INJURYOF THE RAT-KIDNEY - INHIBITION BY A SOLUBLE P-SELECTIN LIGAND/

Ischemia/reperfusion (I/R) injury associated with renal transplantatio n may influence both early graft function and late changes. The initia l (less than or equal to 7 d) events of warm and in situ perfused cold ischemia of native kidneys in uninephrectomized rats were examined. m RNA expression of the early adhesion molecule, E-selectin, peaked with in 6 h; PMNs infiltrated in parallel. T cells and macrophages entered the injured kidney by 2-5 d; the associated upregulation of MHC class II antigen expression suggested increased immunogenicity of the organ. Th1 products (IL-2, TNF alpha, IFN gamma) and macrophage-associated p roducts (IL-1, IL-6, TGF beta) remained highly expressed after 2 d. To examine directly the effects of selectins in I/R injury, a soluble P- selectin glycoprotein ligand (sPSGL) was used, Ischemic kidneys were p erfused in situ with 5 mu g of sPSGL in UW solution; 50 mu g was admin istered intravenously 3 h after reperfusion. E-selectin mRNA remained at baseline, leukocytes did not infiltrate the injured organs througho ut the 7-d period, and their associated products were markedly inhibit ed. Class II expression did not increase. No renal dysfunction seconda ry to I/R occurred. The early changes of I/R injury may be prevented b y treatment with soluble P- and E-selectin ligand. This may reduce sub sequent host inflammatory responses after transplantation.