4.5 Article

Human Pancreatic Islet Preparations Release HMGB1: (Ir)Relevance for Graft Engraftment

期刊

CELL TRANSPLANTATION
卷 22, 期 11, 页码 2175-2186

出版社

SAGE PUBLICATIONS INC
DOI: 10.3727/096368912X657783

关键词

Islet transplantation; Engraftment; High-mobility group box 1 (HMGB1); Human

资金

  1. EU [HEALTH-F5-2009-241883-BetaCellTherapy]
  2. Juvenile Diabetes Research Foundation (JDRF) [6-2006-1098, 31-2008-416, 4-2001-434]

向作者/读者索取更多资源

High levels of donor-derived high-mobility group box 1 (HMGB1) protein have been associated with poor islet graft outcome in mouse models. The aim of our work was to determine whether HMGB1 released by human islets had independent proinflammatory effects that influence engraftment in humans. Human islet preparations contained and released HMGB1 in different amounts, as determined by Western blot and ELISA (median 17 pg/ml/IEQ/24 h; min-max 0-211, n=74). HMGB1 release directly correlated with brain death, donor hyper-amilasemia, and factors related to the pancreas digestion procedure (collagenase and digestion time). HMGB1 release was significantly positively associated with the release of other cytokines/chemokines, particularly with the highly released proinflammatory CXCL8/IL-8, CXCL1/GRO-alpha, and the IFN-gamma-inducible chemokines CXCL10/IP-10 and CXCL9/MIG. HMGB1 release was not modulated by Toll-like receptor 2,3,4,5, and 9 agonists or by exposure to IL-1 beta. When evaluated after islet transplantation, pretransplant HMGB1 release was weakly associated with the activation of the coagulation cascade (evaluated as serum cross-linked fibrin products), but not with the immediate posttransplant inflammatory response. Concordantly, HMGB1 did not affect short-term human islet function. Our data show that human islet HMGB1 release is a sign of damaged islets, although without any independent direct role in graft failure.

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