The specific monocarboxylate transporter-1 (MCT-1) inhibitor, AR-C117977, induces donor-specific suppression, reducing acute and chronic allograft rejection in the rat.

The specific monocarboxylate transporter-1 (MCT-1) inhibitor, AR-C117977, induces donor-specific suppression, reducing acute and chronic allograft rejection in the rat. Research Abstract Details 

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The specific monocarboxylate transporter-1 (MCT-1) inhibitor, AR-C117977, induces donor-specific suppression, reducing acute and chronic allograft rejection in the rat. Abstract Text:

Henrik Ekberg,Zhongquan Qi,Clara Pahlman, Veress,Robert V Bundick,Robert I Craggs,Elain Holness,Susan Edwards,Clare M Murray,Douglas Ferguson,Philip J Kerry,Elaine Wilson,David K Donald,Henrik Ekberg,Zhongquan Qi,Clara Pahlman, Veress,Robert V Bundick,Robert I Craggs,Elain Holness,Susan Edwards,Clare M Murray,Douglas Ferguson,Philip J Kerry,Elaine Wilson,David K Donald,Henrik Ekberg,Zhongquan Qi,Clara Pahlman, Veress,Robert V Bundick,Robert I Craggs,Elain Holness,Susan Edwards,Clare M Murray,Douglas Ferguson,Philip J Kerry,Elaine Wilson,David K Donald,

BACKGROUND: In a search for immunosuppressive drugs having novel mechanisms, monocarboxylate transporter (MCT-1) inhibitors were identified that markedly inhibited immune responses. Here, we report the effects of AR-C117977, a potent MCT-1 inhibitor, on alloimmune responses in the rat. METHODS: In vitro activity was determined in a rat mixed lymphocyte response (MLR). In vivo activity was tested in a graft versus host response (GVHR) and in both high (DA to PVG) and low (PVG to DA) responder cardiac allograft models. To assess induction of donor-specific suppression recipients of allogeneic hearts surviving longer than 100 days received a second transplant either of the same donor strain or a third-party donor strain. Effects on chronic graft rejection were assessed histologically by evaluating vasculopathy in long-term surviving grafts and in an obliterative bronchiolitis (OB) model. RESULTS: AR-C117977 inhibited the rat MLR and was more potent than cyclosporin A (CsA). In the rat GVHR model, AR-C117977 gave a dose-related inhibition. In the high responder cardiac allograft model, graft survival in excess of 100 days was achieved with AR-C117977 compared with 20 days with CsA and all the long-term survivors exhibited donor-specific suppression on retransplantation. In the low responder model, both AR-C117977 and CsA induced survival in excess of 100 days. Histology of the long-term surviving grafts suggested reduced vasculopathy associated with chronic rejection. Furthermore, AR-C117977 inhibited the occlusion of transplanted trachea in a OB model. CONCLUSION: This report describes a MCT-1 specific inhibitor having immunosuppressive activity on alloimmune responses and inducing donor-specific suppression.

The specific monocarboxylate transporter-1 (MCT-1) inhibitor, AR-C117977, induces donor-specific suppression, reducing acute and chronic allograft rejection in the rat. Publishing Authors By Initials

H Ekberg,Z Qi,C Pahlman,B Veress,RV Bundick,RI Craggs,E Holness,S Edwards,CM Murray,D Ferguson,PJ Kerry,E Wilson,DK Donald,H Ekberg,Z Qi,C Pahlman,B Veress,RV Bundick,RI Craggs,E Holness,S Edwards,CM Murray,D Ferguson,PJ Kerry,E Wilson,DK Donald,H Ekberg,Z Qi,C Pahlman,B Veress,RV Bundick,RI Craggs,E Holness,S Edwards,CM Murray,D Ferguson,PJ Kerry,E Wilson,DK Donald,

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The specific monocarboxylate transporter-1 (MCT-1) inhibitor, AR-C117977, induces donor-specific suppression, reducing acute and chronic allograft rejection in the rat. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Transplantation

VOLUME: 84

Page Numbers: 1191-9

Journal Abbreviation: Transplantation

ISSN: 0041-1337

DAY: 15

MONTH: Nov

YEAR: 2007

The specific monocarboxylate transporter-1 (MCT-1) inhibitor, AR-C117977, induces donor-specific suppression, reducing acute and chronic allograft rejection in the rat. Information

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LANGUAGE: eng

NlmUniqueID: 132144

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AFFILIATION: Department of Nephrology and Transplantation, Lund University, University Hospital, Malmo, Sweden. henrik.ekberg@med.lu.se

Country: United States

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MEDLINETA: Transplantation

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