Regulation of pro-apoptotic leucocyte granule serine proteinases by intracellular serpins
Regulation of pro-apoptotic leucocyte granule serine proteinases by intracellular serpins
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DOI：
10.1046/j.1440-1711.1999.00787.x
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发表时间：
1999-02-01
影响因子：
4
通讯作者：
Bird, PI
中科院分区：
文献类型：
--
作者：
Bird, PI
通过将丝氨酸蛋白酶引入细胞质中，可以启动半胱天冬酶的激活和凋亡。细胞毒性淋巴细胞已经进化出至少一种具有特异性促凋亡活性的丝氨酸蛋白酶（颗粒酶B），以及将其递送到靶细胞的机制，最近的证据表明，其他白细胞颗粒蛋白酶如果释放到细胞内部也可能具有杀伤能力。例如，单核细胞/粒细胞蛋白酶组织蛋白酶G可以在体外激活半胱天蛋白酶，如果其进入细胞是由细菌成孔蛋白介导的，则会诱导细胞凋亡。颗粒酶B和组织蛋白酶G的强促凋亡活性表明，如果涉及包装、脱颗粒或靶向的系统失败并允许蛋白酶进入宿主细胞质，产生这些（或其他）蛋白酶的细胞将面临自我诱导死亡的风险。本综述的目的是描述一组细胞内丝氨酸蛋白酶抑制剂（serpins）的最新工作，这些抑制剂可能在白细胞中起作用，以防止丝氨酸蛋白酶颗粒诱导的自溶。
Caspase activation and apoptosis can be initiated by the introduction of serine proteinases into the cytoplasm of a cell. Cytotoxic lymphocytes have evolved at least one serine proteinase with specific pro-apoptotic activity (granzyme B), as well as the mechanisms to deliver it into a target cell, and recent evidence suggests that other leucocyte granule proteinases may also have the capacity to kill if released into the interior of cells. For example, the monocyte/granulocyte proteinase cathepsin G can activate caspases in vitro, and will induce apoptosis if its entry into cells is mediated by a bacterial pore-forming protein. The potent pro-apoptotic activity of granzyme B and cathepsin G suggests that cells producing these (or other) proteinases would be at risk from self-induced death if the systems involved in packaging, degranulation or targeting fail and allow proteinases to enter the host cell cytoplasm. The purpose of the present review is to describe recent work on a group of intracellular serine proteinase inhibitors (serpins) which may function in leucocytes to prevent autolysis induced by the granule serine proteinases.