Selectin Blockade Plus Therapy with Low‐Dose Sirolimus and Cyclosporin A Prevent Brain Death‐Induced Renal Allograft Dysfunction

Both antigen‐dependent and ‐independent factors influence long‐term organ allograft function and survival. Brain death (BD), a significant antigen‐independent, donor‐related injury upregulates a variety of inflammatory mediators in peripheral organs. One of the earliest responses to such an insult is the expression of selectins by endothelial cells of the transplanted tissues; these in turn trigger a cascade of nonspecific events, that enhance host alloresponses and which may be worsened by toxic effects of long‐term immunosuppression. Using a rat model in which donor BD accentuates subsequent renal allograft injury, we have tested the effects of therapy with recombinant P‐selectin glycoprotein ligand (rPSGL‐Ig) alone, or in combination with sirolimus (SRL) and cyclosporin A. We found that in contrast to the effects of standard doses of SRL or cyclosporine, rPSGL‐Ig decreased inflammation in the early posttransplant period such that lower doses of maintenance immunosuppression were sufficient to maintain long‐term graft function.

• Publication year

  2005

• Venue

  American Journal of Transplantation

• Publication date

  2005-04-01

• Fields of study

  Medicine

• Identifiers
  DOI 10.1111/j.1600-6143.2005.00763.xPMID 15760389
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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