2246 CCR5/CXCR3 BLOCKADE PROLONGED KIDNEY ALLOGRAFT SURVIVAL WITH OR WITHOUT CYCLOSPORINE VIA THE INHIBITION OF T CELL AND MACROPHAGE RECRUITMENT

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You have accessJournal of UrologyTransplantation & Vascular Surgery: Renal Transplantation, Vascular Surgery1 Apr 20112246 CCR5/CXCR3 BLOCKADE PROLONGED KIDNEY ALLOGRAFT SURVIVAL WITH OR WITHOUT CYCLOSPORINE VIA THE INHIBITION OF T CELL AND MACROPHAGE RECRUITMENT Yoichi Kakuta, Masayoshi Okumi, Koichi Tsutahara, Toyofumi Abe, Koji Yazawa, Katsuyoshi Matsunami, Shuji Miyagawa, Shiro Takahara, and Norio Nonomura Yoichi KakutaYoichi Kakuta Suita, Japan More articles by this author , Masayoshi OkumiMasayoshi Okumi Suita, Japan More articles by this author , Koichi TsutaharaKoichi Tsutahara Suita, Japan More articles by this author , Toyofumi AbeToyofumi Abe Suita, Japan More articles by this author , Koji YazawaKoji Yazawa Suita, Japan More articles by this author , Katsuyoshi MatsunamiKatsuyoshi Matsunami Hiroshima, Japan More articles by this author , Shuji MiyagawaShuji Miyagawa Suita, Japan More articles by this author , Shiro TakaharaShiro Takahara Suita, Japan More articles by this author , and Norio NonomuraNorio Nonomura Suita, Japan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.2488AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES In renal transplantation, the acute allograft rejection episodes is a major determinant of graft survival. In the cell-mediated rejection, a chemokine-chemokine receptor interactions is a key functional events in T cell recruitment and has attracted deep interest to potential therapeutic targets. We investigated the effects of CCR5/CXCR3 blockade in a rat kidney allotransplantation model. METHODS Left kidneys from male Dark Agouti rats were orthotopically transplanted into bilaterally nephrectomized male Lewis rats. Rats were treated with 10 mg/kg CCR5/CXCR3 blockde from day 0 to 14 (or until rejection) and 2.0 mg/kg cyclosporine (CsA) from day 0 to 5. The treatment groups were as follow: control group (n=7); treated with PBS, chemokine receptor blockade (CRB) group (n=6); treated with CCR5/CXCR3 blockade alone, CsA group (n=6); treated with CsA alone, combined therapy (CT) group (n=5); treated with both CCR5/CXCR3 blockade and CsA. RESULTS While the median survival time (MST) of the control group was 6.5 days, the MST of CRB group was 8.0 days (p<0.05 vs. control group). Compared with CsA group (MST: 9.0 days), the survival time of CT group was extremely prolonged (MST: 42.0 days, p<0.05 vs. CsA group) as shown in Figure. Pathological analysis revealed less signs of acute rejection in CRB, with significantly less numbers of CD4+, CD8+, and CCR5+ T cells compared with the control. There was no sing of acute rejection in CT group in day 5. RT-PCR examinations showed significant decrease in IFN-gamma, and IL-2 in CRB group, with no change of IL-4, or IL-17. Additionaly, when we evaluated the infiltration of macrophage, which act as effector cells in acute rejection, by ED-1 staining, the number of ED-1+ cells were significantly less in CRB group than those in control group. The expression of IL-18 was significantly less in CRB group. CONCLUSIONS Treatmant with CCR5/CXCR3 blockade prolonged allograft survival in a rat kidney transplantation model with or without cyclosporine, by preventing intragraft infiltration of T cell and macrophage. Further exploration of these effects will provide the novel treatment of the kidney allograft transplantation. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e901 Peer Review Report Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Yoichi Kakuta Suita, Japan More articles by this author Masayoshi Okumi Suita, Japan More articles by this author Koichi Tsutahara Suita, Japan More articles by this author Toyofumi Abe Suita, Japan More articles by this author Koji Yazawa Suita, Japan More articles by this author Katsuyoshi Matsunami Hiroshima, Japan More articles by this author Shuji Miyagawa Suita, Japan More articles by this author Shiro Takahara Suita, Japan More articles by this author Norio Nonomura Suita, Japan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...