Human Pancreatic Islet Preparations Release HMGB1: (Ir)Relevance for Graft Engraftment
Human Pancreatic Islet Preparations Release HMGB1: (Ir)Relevance for Graft Engraftment
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DOI：
10.3727/096368912x657783
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发表时间：
2013-01-01
影响因子：
3.3
通讯作者：
Piemonti, Lorenzo
中科院分区：
文献类型：
--
作者：
Nano, Rita;Racanicchi, Leda;Piemonti, Lorenzo
在小鼠模型中，高水平的供体来源的高迁移率族蛋白盒1（HMGB 1）蛋白与较差的胰岛移植结果相关。我们工作的目的是确定人类胰岛释放的HMGB 1是否具有影响人类植入的独立促炎作用。人胰岛制备物含有和释放不同量的HMGB 1，如通过蛋白质印迹和ELISA测定的（中值17 pg/ml/IEQ/24 h;最小值-最大值0-211，n=74）。HMGB 1的释放与脑死亡、供体高淀粉酶血症以及与胰腺消化过程相关的因素（胶原酶和消化时间）直接相关。HMGB 1释放与其他细胞因子/趋化因子的释放显著正相关，特别是与高度释放的“促炎”CXCL 8/IL-8、CXCL 1/GRO-α和IFN-γ诱导型趋化因子CXCL 10/IP-10和CXCL 9/IL-10。HMGB 1的释放不受Toll样受体2、3、4、5和9激动剂或暴露于IL-1 β的调节。胰岛移植后评价时，移植前HMGB 1释放与凝血级联反应（评价为血清交联纤维蛋白产物）的激活弱相关，但与移植后即刻炎症反应无关。与此一致，HMGB 1不影响短期人类胰岛功能。我们的数据表明，人胰岛HMGB 1的释放是胰岛“受损”的标志，尽管在移植失败中没有任何独立的直接作用。
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.