Abstract |
Chemokines are thought to contribute to the cellular infiltrate characteristic of renal transplant rejection. We show that Met-RANTES, a chemokine receptor antagonist, suppresses recruitment of inflammatory cells into renal allografts. In a renal transplant model (Fisher RT1(lvl) rat kidney into Lewis RT1(l) rat) where no additional immune suppressant was used, Met-RANTES-treated animals showed a significant reduction in vascular injury score (16.10 +/- 5.20 vs. 62.67 +/- 18.64) and tubular damage score (15.70 +/- 5.22 vs. 33.00 +/- 6.44) relative to untreated animals. In a more severe rejection model (Brown-Norway RT1(n) rat kidney into Lewis RT1(1) rat), Met-RANTES significantly augmented low-dose cyclosporin A treatment to reduce all aspects of renal injury including interstitial inflammation (score 71.00 +/- 6.10 vs. 157.30 +/- 21.30). The majority of infiltrating cells in these models (60-70%) consisted of monocytes. Potential mechanisms of action of Met-RANTES were tested using monocyte attachment assays on microvascular endothelium under physiological flow conditions. Preexposure of microvascular endothelium to RANTES resulted in RANTES immobilization and RANTES-induced firm adhesion of monocytes only after prestimulation of the endothelium with IL-1beta. Met-RANTES completely inhibited this RANTES-mediated arrest. Thus, Met-RANTES may counter acute rejection by blocking leukocyte firm adhesion to inflamed endothelium.
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Authors | H J Gröne, C Weber, K S Weber, E F Gröne, T Rabelink, C M Klier, T N Wells, A E Proudfood, D Schlöndorff, P J Nelson |
Journal | FASEB journal : official publication of the Federation of American Societies for Experimental Biology
(FASEB J)
Vol. 13
Issue 11
Pg. 1371-83
(Aug 1999)
ISSN: 0892-6638 [Print] United States |
PMID | 10428761
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Chemokine CCL5
- Immunosuppressive Agents
- RANTES, Met-
- Cyclosporine
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Topics |
- Animals
- Chemokine CCL5
(analogs & derivatives, immunology)
- Cyclosporine
(administration & dosage)
- Endothelium, Vascular
(immunology, pathology)
- Graft Rejection
(immunology, prevention & control)
- Humans
- Immunosuppressive Agents
(administration & dosage)
- Kidney Transplantation
- Kidney Tubules
(immunology, pathology)
- Male
- Monocytes
(immunology, pathology)
- Rats
- Rats, Inbred BN
- Rats, Inbred F344
- Rats, Inbred Lew
- Transplantation Immunology
- Transplantation, Homologous
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