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The specific monoca...
The specific monocarboxylate transporter-1 (MCT-1) inhibitor, AR-C117977, induces donor-specific suppression, reducing acute and chronic allograft rejection in the rat
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- Ekberg, Henrik (author)
- Lund University,Lunds universitet,Enheten för forskning kring njurfunktion och njursjukdom,Kirurgi,Forskargrupper vid Lunds universitet,Renal Research Unit,Surgery,Lund University Research Groups
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Qi, Zhongquan (author)
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Pahlman, Clara (author)
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Veress, Bela (author)
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Bundick, Robert V. (author)
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Craggs, Robert I. (author)
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Holness, Elain (author)
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Edwards, Susan (author)
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Murray, Clare M. (author)
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Ferguson, Douglas (author)
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Kerry, Philip J. (author)
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Wilson, Elaine (author)
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Donald, David K. (author)
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(creator_code:org_t)
- Ovid Technologies (Wolters Kluwer Health), 2007
- 2007
- English.
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In: Transplantation. - : Ovid Technologies (Wolters Kluwer Health). - 1534-6080 .- 0041-1337. ; 84:9, s. 1191-1199
- Related links:
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http://www.transplan...
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http://dx.doi.org/10...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Subject headings
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- 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 (013) 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 013 model. Conclusion. This report describes a MCT-1 specific inhibitor having immunosuppressive activity on alloinimune responses and inducing donor-specific suppression.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kirurgi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Surgery (hsv//eng)
Keyword
- donor-specific suppression
- alloimmune responses
- immunosuppression
- monocarboxylate transporter
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Ekberg, Henrik
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Qi, Zhongquan
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Pahlman, Clara
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Veress, Bela
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Bundick, Robert ...
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Craggs, Robert I ...
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show more...
-
Holness, Elain
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Edwards, Susan
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Murray, Clare M.
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Ferguson, Dougla ...
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Kerry, Philip J.
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Wilson, Elaine
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Donald, David K.
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Surgery
- Articles in the publication
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Transplantation
- By the university
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Lund University