Berthou C, Zhang Y, Sasportes M
Unité INSERM 462, Hôpital Saint-Louis, Paris, France.
Pathol Biol (Paris). 1998 Oct;46(8):617-24.
Granzyme B is a serine protease produced by cytotoxic lymphocytes and capable of inducing rapid target cell death by apoptosis. This effect was found to be closely correlated with the presence of perforin, or pore-forming protein, also contained in the cytoplasmic granules of cytotoxic lymphocytes. Subsequent data suggested that the chief role of perforin is to facilitate accessibility of granzyme B to its cytoplasmic and nuclear targets. Granzyme B may penetrate within the cytoplasm autonomously via a membrane receptor expressed by the target cell, before entering endocytic vesicles containing the protein. Granzyme B can induce target cell death via two complementary pathways, a cytosolic pathway involving cascade activation of proapoptotic caspases, and a nuclear pathway probably involving a cell cycle regulating protein and/or kinase Cdc2 activation. Recent data have established that non-lymphoid cells, including human epithelial cells, can express granzyme B and release it into the extracellular space during the repair process following disruption of the epidermal barrier. This results in local anti-infectious activity that compensates for the break in the mechanical skin barrier and may be a component of natural immunity.
颗粒酶B是一种由细胞毒性淋巴细胞产生的丝氨酸蛋白酶，能够通过凋亡诱导靶细胞快速死亡。发现这种效应与穿孔素（一种也存在于细胞毒性淋巴细胞胞质颗粒中的成孔蛋白）的存在密切相关。随后的数据表明，穿孔素的主要作用是促进颗粒酶B接近其胞质和核靶点。颗粒酶B可能通过靶细胞表达的膜受体自主穿透进入细胞质，然后进入含有该蛋白的内吞小泡。颗粒酶B可通过两条互补途径诱导靶细胞死亡，一条是涉及促凋亡半胱天冬酶级联激活的胞质途径，另一条是可能涉及细胞周期调节蛋白和/或激酶Cdc2激活的核途径。最近的数据表明，包括人类上皮细胞在内的非淋巴细胞在表皮屏障破坏后的修复过程中可以表达颗粒酶B并将其释放到细胞外空间。这导致局部抗感染活性，补偿了皮肤机械屏障的破损，可能是天然免疫的一个组成部分。
