Heissig Beate, Ohki Makiko, Ishihara Makoto, Tashiro Yoshihiko, Nishida Chiemi, Gritli Ismael, Rosenkvist Jeanette, Hattori Koichi
Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
J Cell Physiol. 2009 Dec;221(3):521-5. doi: 10.1002/jcp.21897.
Hematopoietic stem cells (HSCs) can differentiate and proliferate in response to hematopoietic stress (e.g., myelosuppression, infections, and allergic reactions), thereby ensuring a well-regulated supply of mature and immature hematopoietic cells within the circulation and prompt adjustment of blood cell levels within normal ranges. The recovery of tissues and organs from hematopoietic stress (e.g., myelosuppression or ionizing irradiation) is dependent on two cell types: resident HSCs which repopulate the bone marrow (BM) cavity, and stromal cells. BM regeneration critically depends on the release of soluble factors from cells such as stromal cells, a process regulated by proteases. Two proteolytic systems, the fibrinolytic system and the matrix metalloproteinases (MMPs), have recently been shown to be involved in this process (Heissig B, 2007, Cell Stem Cell 1: 658-670). The plasminogen/plasmin system is mostly recognized for its fibrinolytic activity, but it is also involved in processes such as cell invasion, chemotaxis, growth factor activity modulation, and tissue remodeling. This review focuses on the role of plasmin and its activators as key players in controlling the hematopoietic stress response after myelosuppression (hematopoietic regeneration). Aspects of plasmin regulation, especially regulation of its ability to activate MMPs and the functional consequences of this enzyme activation, such as plasmin-mediated release of biologically relevant cytokines from the matrix and cell surfaces, will be discussed.
造血干细胞（HSCs）能够响应造血应激（如骨髓抑制、感染和过敏反应）而分化和增殖，从而确保循环系统中成熟和未成熟造血细胞的供应得到良好调节，并使血细胞水平迅速调整至正常范围。组织和器官从造血应激（如骨髓抑制或电离辐射）中恢复依赖于两种细胞类型：重新填充骨髓腔的驻留造血干细胞和基质细胞。骨髓再生严重依赖于基质细胞等细胞释放可溶性因子，这一过程由蛋白酶调节。最近发现两种蛋白水解系统，即纤维蛋白溶解系统和基质金属蛋白酶（MMPs）参与了这一过程（Heissig B，2007，《细胞干细胞》1：658 - 670）。纤溶酶原/纤溶酶系统主要因其纤维蛋白溶解活性而被认识，但它也参与细胞侵袭、趋化性、生长因子活性调节和组织重塑等过程。本综述重点关注纤溶酶及其激活剂在控制骨髓抑制后造血应激反应（造血再生）中的关键作用。将讨论纤溶酶调节的各个方面，特别是其激活MMPs能力的调节以及这种酶激活的功能后果，如纤溶酶介导的从基质和细胞表面释放生物学相关细胞因子。
