The cytokine-adhesion molecule cascade in ischemia/reperfusion injury of the rat kidney. Inhibition by a soluble P-selectin ligand

J Clin Invest. 1997 Jun 1;99(11):2682-90. doi: 10.1172/JCI119457.


Ischemia/reperfusion (I/R) injury associated with renal transplantation may influence both early graft function and late changes. The initial (</= 7 d) events of warm and in situ perfused cold ischemia of native kidneys in uninephrectomized rats were examined. mRNA expression of the early adhesion molecule, E-selectin, peaked within 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, TNFalpha, IFNgamma) and macrophage-associated products (IL-1, IL-6, TGFbeta) 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 perfused in situ with 5 microg of sPSGL in UW solution; 50 microg was administered intravenously 3 h after reperfusion. E-selectin mRNA remained at baseline, leukocytes did not infiltrate the injured organs throughout the 7-d period, and their associated products were markedly inhibited. Class II expression did not increase. No renal dysfunction secondary to I/R occurred. The early changes of I/R injury may be prevented by treatment with soluble P- and E-selectin ligand. This may reduce subsequent host inflammatory responses after transplantation.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Adhesion Molecules / metabolism
  • Cytokines / antagonists & inhibitors
  • Cytokines / metabolism*
  • Kidney / metabolism
  • Kidney / pathology*
  • Ligands
  • Male
  • Membrane Glycoproteins / pharmacology*
  • P-Selectin / metabolism
  • Rats
  • Rats, Inbred Lew
  • Reperfusion Injury / metabolism*


  • Cell Adhesion Molecules
  • Cytokines
  • Ligands
  • Membrane Glycoproteins
  • P-Selectin
  • P-selectin ligand protein