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Met‐RANTES reduces vascular and tubular damage during acute renal transplant rejection: blocking monocyte arrest and recruitment
Author(s) -
Gröne HermannJosef,
Weber Christian,
Weber Kim S. C.,
Gröne Elisabeth F.,
Rabelink Ton,
Klier Christiane M.,
Wells Timothy N. C.,
Proudfoot Amanda E.,
Schlondorff Detlef,
Nelson Peter J.
Publication year - 1999
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.13.11.1371
Subject(s) - chemokine , monocyte , medicine , endothelium , chemokine receptor , kidney , inflammation , immunology , pharmacology
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 RTI 1 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 micro‐vascular endothelium to RANTES resulted in RANTES immobilization and RANTES‐induced firm adhesion of monocytes only after prestimulation of the endothelium with IL‐1β. Met‐RANTES completely inhibited this RANTES‐mediated arrest. Thus, Met‐RANTES may counter acute rejection by blocking leukocyte firm adhesion to inflamed endothelium.—Gröne, H.‐J., Weber, C., Weber, K. S. C., Gröne, E. F., Rabelink, T., Klier, C. M., Wells, T. N. C., Proudfoot, A. E., Schlöndorff, D., Nelson, P. J. Met‐RANTES reduces vascular and tubular damage during acute renal transplant rejection: blocking monocyte arrest and recruitment. FASEB J. 13, 1371–1383 (1999)