Mature hepatocyte growth factor/scatter factor on the surface of human granulocytes is released by a mechanism involving activated factor Xa
Mature hepatocyte growth factor/scatter factor on the surface of human granulocytes is released by a mechanism involving activated factor Xa
复制标题
DOI：
10.4049/jimmunol.176.11.6945
复制
发表时间：
2006-06-01
影响因子：
4.4
通讯作者：
Matsuguchi, Tetsuya
中科院分区：
文献类型：
--
作者：
Ohnishi, Tomokazu;Kakimoto, Kyoko;Matsuguchi, Tetsuya
血清肝细胞生长因子（HGF）在患有包括动脉闭塞性疾病在内的各种组织损伤的患者中迅速升高。然而，HGF增加的细胞来源在很大程度上仍然未知。在本研究中，我们发现，生物活性成熟的肝细胞生长因子是组成型存在于人外周血中的粒细胞表面。外源性加入的I-125标记的碘-HGF有效地结合到粒细胞表面，而在粒细胞中仅检测到少量的HGF mRNA，表明粒细胞上的成熟HGF可能来自其他细胞类型。有趣的是，用人血清处理粒细胞迅速诱导细胞表面相关HGF的释放。在体内，促凝血酶原激酶注射到小鼠中增加了HGF从移植的人粒细胞的释放，这被抑制预处理与因子Xa的特异性抑制剂DX9065 a。此外，DX9065 a还在体外抑制血清诱导的人粒细胞的HGF释放，表明血清中的HGF释放因子与因子Xa活化相关。因此，人粒细胞可以在外周血中充当HGF的转运蛋白，在由血液凝固引起的损伤部位释放HGF，其中HGF可以促进组织修复。
Serum hepatocyte growth factor (HGF) is rapidly increased in patients suffering from various tissue injuries including arterial occlusive diseases. However, the cellular sources of the HGF increase remain largely unknown. In the present study, we showed that bioactive mature HGF is constitutively present on the surface of granulocytes in human peripheral blood. Exogenously added I-125-labeled iodo-HGF efficiently bound to granulocyte surface, whereas only a scarce amount of HGF mRNA was detected in granulocytes, indicating that the mature HGF on granulocytes is likely to be derived from other cell types. Interestingly, treatment of granulocytes with human serum rapidly induced the release of the cell surface-associated HGF. In vivo, thromboplastin injection into mice increased HGF release from transplanted human granulocytes, which was inhibited by the pretreatment with DX9065a, a specific inhibitor of factor Xa. Furthermore, DX9065a also inhibited the serum-induced HGF release from human granulocytes in vitro, suggesting that the HGF-releasing factor(s) in serum is associated with factor Xa activation. Thus, human granulocytes may function as a transporter of HGF in the peripheral blood, releasing HGF at the injured sites caused by blood coagulation, where HGF may promote tissue repair.