The N-terminal domain of thrombomodulin sequesters high-mobility group-B1 protein, a novel antiinflammatory mechanism
The N-terminal domain of thrombomodulin sequesters high-mobility group-B1 protein, a novel antiinflammatory mechanism
复制标题
DOI：
10.1172/jci200522782
复制
发表时间：
2005-05-01
影响因子：
15.9
通讯作者：
Maruyama, I
中科院分区：
文献类型：
--
作者：
Abeyama, K;Stern, DM;Maruyama, I
血栓调节蛋白(TM)是一种内皮抗凝辅助因子，可促进凝血酶介导的活化蛋白C(APC)的形成。我们发现TM的N端凝集素样结构域(131)具有独特的抗炎特性。TM通过Di与高迁移率族B1DNA结合蛋白(HMGB I)结合，HMGB I是一种在从细胞核释放后与坏死细胞损伤密切相关的因子，从而在体外阻止了紫外线辐射诱导的白细胞激活。皮肤炎症和体内脂多糖诱导的致死性。我们的数据还显示了一种跨越TM的D1的多肽的抗炎特性，并暗示了其治疗潜力。这些发现突出了一种新的机制，即隔离介质，通过这种机制，内皮辅因子TM明显地抑制炎症与其抗凝血辅因子活性，从而阻止这些介质与血管系统中效应细胞上的细胞表面受体相互作用。
Thrombomodulin (TM) is an endothelial anticoagulant cofactor that promotes thrombin-mediated formation of activated protein C (APC). We have found that the N-terminal lectin-like domain (131) of TM has unique antiinflammatory properties. TM, via D I, binds high-mobility group-B1 DNA-binding protein (HMGB I), a factor closely associated with necrotic cell damage following its release from the nucleus, thereby preventing in vitro leukocyte activation, in vivo UV irradiation-induced. cutaneous inflammation, and in vivo lipopolysaccharide-induced lethality. Our data also demonstrate antiinflammatory properties of a peptide spanning D1 of TM and suggest its therapeutic potential. These findings highlight a novel mechanism, i.e., sequestration of mediators, through which an endothelial cofactor, TM, suppresses inflammation quite distinctly from its anticoagulant cofactor activity, thereby preventing the interaction of these mediators with cell surface receptors on effector cells in the vasculature.