A Metabolomic Approach ((1)H HRMAS NMR Spectroscopy) Supported by Histology to Study Early Post-transplantation Responses in Islet-transplanted Livers.
Fiche publication
Date publication
janvier 2016
Journal
International journal of biological sciences
Auteurs
Membres identifiés du Cancéropôle Est :
Pr NAMER Izzie-Jacques, Pr GIES Jean-Pierre
Tous les auteurs :
Vivot K, Benahmed MA, Seyfritz E, Bietiger W, Elbayed K, Ruhland E, Langlois A, Maillard E, Pinget M, Jeandidier N, Gies JP, Namer IJ, Sigrist S, Reix N
Lien Pubmed
Résumé
Intrahepatic transplantation of islets requires a lot of islets because more than 50% of the graft is lost during the 24 hours following transplantation. We analyzed, in a rat model, early post-transplantation inflammation using systemic inflammatory markers, or directly in islet-transplanted livers by immunohistochemistry. (1)H HRMAS NMR was employed to investigate metabolic responses associated with the transplantation. Inflammatory markers (Interleukin-6, α2-macroglobulin) are not suitable to follow islet reactions as they are not islet specific. To study islet specific inflammatory events, immunohistochemistry was performed on sections of islet transplanted livers for thrombin (indicator of the instant blood-mediated inflammatory reaction (IBMIR)) and granulocytes and macrophages. We observed a specific correlation between IBMIR and granulocyte and macrophage infiltration after 12 h. In parallel, we identified a metabolic response associated with transplantation: after 12 h, glucose, alanine, aspartate, glutamate and glutathione were significantly increased. An increase of glucose is a marker of tissue degradation, and could be explained by immune cell infiltration. Alanine, aspartate and glutamate are inter-connected in a common metabolic pathway known to be activated during hypoxia. An increase of glutathione revealed the presence of antioxidant protection. In this study, IBMIR visualization combined with (1)H HRMAS NMR facilitated the characterization of cellular and molecular pathways recruited following islet transplantation.
Mots clés
1H NMR, histology, islet transplantation, liver., metabolomics
Référence
Int. J. Biol. Sci.. 2016 ;12(10):1168-1180