Abstract | BACKGROUND: Initial insults to kidney allografts, characterized by infiltration of mononuclear inflammatory cells, contribute to chronic allograft nephropathy. Chemokines such as RANTES (regulated upon activation, normal T cell expressed) are thought to be responsible for the recruitment and activation of infiltrating cells. The present study investigated whether early application of Met-RANTES, a chemokine receptor antagonist that blocks the effects of RANTES, can protect renal allografts from long-term deterioration. METHODS: Fisher (F344) rat kidneys were orthotopically transplanted into Lewis recipients and treated with cyclosporine A (1.5 mg/kg/day) for the first 10 days following transplantation, together with either Met-RANTES at 40 microg/day, 200 microg/day or vehicle for the first 7 days. Animals were harvested at 2 and 28 weeks after transplantation for histologic, immunohistologic and molecular analysis. RESULTS: CONCLUSIONS: Blockade of chemokine receptors by Met-RANTES diminishes early infiltration and activation of mononuclear cells in the grafts, and thus reduces the pace of chronic allograft nephropathy.
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Authors | Erwei Song, Hequn Zou, Yousheng Yao, Amanda Proudfoot, Balazs Antus, Shanying Liu, Lutz Jens, Uwe Heemann |
Journal | Kidney international
(Kidney Int)
Vol. 61
Issue 2
Pg. 676-85
(Feb 2002)
ISSN: 0085-2538 [Print] United States |
PMID | 11849411
(Publication Type: Journal Article)
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Chemical References |
- Chemokine CCL5
- Interleukin-1
- Interleukin-2
- RANTES, Met-
- RNA, Messenger
- Tumor Necrosis Factor-alpha
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Topics |
- Animals
- Atrophy
- Blood Pressure
- Body Weight
- Cell Division
(drug effects)
- Chemokine CCL5
(analogs & derivatives, genetics, pharmacology)
- Fibrosis
- Gene Expression
(immunology)
- Glomerulosclerosis, Focal Segmental
(drug therapy, immunology, surgery)
- Graft Rejection
(drug therapy, immunology, pathology)
- Graft Survival
(drug effects, immunology)
- Interleukin-1
(genetics)
- Interleukin-2
(genetics)
- Kidney Transplantation
- Kidney Tubules
(pathology)
- Leukocytes
(immunology)
- Male
- RNA, Messenger
(analysis)
- Rats
- Rats, Inbred F344
- Transplantation, Homologous
- Tumor Necrosis Factor-alpha
(genetics)
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