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Selectin Blockade Plus Therapy with Low‐Dose Sirolimus and Cyclosporin A Prevent Brain Death‐Induced Renal Allograft Dysfunction
Author(s) -
Gasser Martin,
WaagaGasser Ana Maria,
Grimm Michael W.,
Grimm Martin R.,
Lenhard Miriam S.,
Kistvan Holthe Joana E.,
Laskowski Igor,
Shaw Gray D.,
Thiede Arnulf,
Hancock Wayne W.,
Tilney Nicholas L.
Publication year - 2005
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/j.1600-6143.2005.00763.x
Subject(s) - medicine , immunosuppression , sirolimus , inflammation , immunology , transplantation , kidney , pharmacology
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.