HMGB1 release in co-cultures of porcine endothelial and human T cells
HMGB1 release in co-cultures of porcine endothelial and human T cells
复制标题
DOI：
10.1111/j.1399-3089.2007.00434.x
复制
发表时间：
2007-11-01
影响因子：
3.9
通讯作者：
Maruyama, Ikuro
中科院分区：
文献类型：
--
作者：
Kawahara, Ko-Ichi;Setoyama, Kentaro;Maruyama, Ikuro
高迁移率族蛋白-1（HMGB 1）蛋白主要来自细胞核，通过坏死或受损细胞被动或通过单核细胞/巨噬细胞分泌主动释放到细胞外环境中。细胞外HMGB 1通过促进细胞因子（例如，肿瘤坏死因子-α）产生而充当有效的炎症刺激物，并且还具有促凝血活性。由晚期糖基化终产物受体（HMGB 1受体）启动的信号传导途径也诱导补体激活。最近的研究表明，HMGB 1与心脏移植急性排斥反应有关，并已确定浸润性T细胞和其他受损细胞是其主要来源。使用抗HMGB 1抗体HMGB 1 box-A（氨基末端区域）和可溶性精氨酸阻断HMGB 1可使小鼠免于急性排斥反应。因此，我们研究了猪主动脉内皮细胞（PAEC）和人白细胞的共培养物中HMGB 1的释放。人T细胞，而不是B细胞，单核细胞或中性粒细胞，刺激显着的HMGB 1释放与PAEC培养;这种活动需要细胞-细胞接触，是剂量依赖性的，通过蛋白质印迹法测定。释放的HMGB 1来自两种细胞类型，免疫荧光显微镜显示，它存在于与T细胞接触的PAEC的胞质溶胶中，并从T细胞核中消失。这些结果表明，PAEC和T细胞之间的直接相互作用可能是触发HMGB 1释放的关键因素，这表明HMGB 1与早期移植排斥反应有关。
High mobility group box-1 (HMGB1) protein, primarily from the nucleus, is released into the extracellular milieu either passively by necrotic or damaged cells, or actively by secretion from monocytes/macrophages. Extracellular HMGB1 acts as a potent inflammatory stimulator by promoting cytokine (for example, tumor necrosis factor-alpha) production, and also has pro-coagulant activity. The signaling pathway initiated by receptor for advanced glycation end-product (RAGE), which is the HMGB1 receptor, also induces complement activation. Recent studies have implicated HMGB1 in acute cardiac allograft rejection, and have identified infiltrating T cells and other damaged cells as its main sources. HMGB1 blockade using the anti-HMGB1 antibody HMGB1 box-A (amino-terminal region) and soluble RAGE rescues mice from acute rejection. We therefore studied the release of HMGB1 in co-cultures of porcine aortic endothelial cells (PAEC) and human leukocytes. Human T cells, but not B cells, monocytes or neutrophils, stimulated significant HMGB1 release in culture with PAEC; this activity required cell-cell contact and was dose-dependent, as determined by Western blotting. The released HMGB1 originated from both cell types, as immunofluorescent microscopy showed that it was present in the cytosol of PAEC in contact with T cells, and had disappeared from the T-cell nuclei. These results demonstrate that direct interactions between PAEC and T cells might be a key factor in triggering HMGB1 release, which suggests that HMGB1 is associated with graft rejection in the early phase.