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  • Title: [Reduction of acute kidney transplantation rejection by the chemokine receptor antagonist Met-RANTES].
    Author: Gröne HJ, Weber C, Weber KS, Gröne EF, Klier CM, Wells TN, Proudfoot AE, Schlöndorff D, Nelson PJ.
    Journal: Verh Dtsch Ges Pathol; 1999; 83():205-11. PubMed ID: 10714211.
    Abstract:
    Chemokines contribute to the mononuclear cell infiltrate in vessels and interstitium which is characteristic of renal transplant rejection. By employing the chemokine receptor blocker Met-RANTES it was shown that recruitment of inflammatory cells into renal allografts could be significantly suppressed. In a renal transplant model (Fisher RT1(1v1) rat kidney into Lewis RT1(1) rat) 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 severe rejection model (Brown-Norway RT1n 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). In a monocyte attachment assay on microvascular endothelium under physiological flow conditions exposure of microvascular endothelium to RANTES resulted in RANTES immobilization and RANTES-induced firm adhesion of monocytes only after prestimulation of the endothelium with IL-1 beta. Met-RANTES completely inhibited this RANTES-mediated arrest. Thus, Met-RANTES can reduce acute rejection by impeding leukocyte arrest to inflamed endothelium.
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