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Citro, A.* ; Cantarelli, E.* ; Maffi, P.* ; Nano, R.* ; Melzi, R.* ; Mercalli, A.* ; Dugnani, E.* ; Sordi, V.* ; Magistretti, P.* ; Daffonchio, L.* ; Ruffini, P.A.* ; Allegretti, M.* ; Secchi, A.* ; Bonifacio, E.* ; Piemonti, L.*

CXCR1/2 inhibition enhances pancreatic islet survival after transplantation.

J. Clin. Invest. 122, 3647-3651 (2012)
DOI Verlagsversion bestellen
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Although long considered a promising treatment option for type 1 diabetes, pancreatic islet cell transformation has been hindered by immune system rejection of engrafted tissue. The identification of pathways that regulate post-transplant detrimental inflammatory events would improve management and outcome of transplanted patients. Here, we found that CXCR1/2 chemokine receptors and their ligands are crucial negative determinants for islet survival after transplantation. Pancreatic islets released abundant CXCR1/2 ligands (CXCL1 and CXCL8). Accordingly, intrahepatic CXCL1 and circulating CXCL1 and CXCL8 were strongly induced shortly after islet infusion. Genetic and pharmacological blockade of the CXCL1-CXCR1/2 axis in mice improved intrahepatic islet engraftment and reduced intrahepatic recruitment of polymorphonuclear leukocytes and NKT cells after islet infusion. In humans, the CXCR1/2 allosteric inhibitor reparixin improved outcome in a phase 2 randomized, open-label pilot study with a single infusion of allogeneic islets. These findings indicate that the CXCR1/2-mediated pathway is a regulator of islet damage and should be a target for intervention to improve the efficacy of transplantation.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
ISSN (print) / ISBN 0021-9738
e-ISSN 1558-8238
Quellenangaben Band: 122, Heft: 10, Seiten: 3647-3651 Artikelnummer: , Supplement: ,
Verlag American Society of Clinical Investigation
Begutachtungsstatus Peer reviewed
Institut(e) Institute for Pancreatic Beta Cell Research (IPI)