Froelich Christopher J, Pardo Julian, Simon Markus M
Department of Medicine, NorthShore University HealthSystem Research Institute, Evanston, IL, 60201, USA.
Trends Immunol. 2009 Mar;30(3):117-23. doi: 10.1016/j.it.2009.01.002. Epub 2009 Feb 13.
The cytotoxic cell granule secretory pathway is viewed as indispensable for eliminating tumor and virally infected cells through a process in which the pore-forming protein, perforin, delivers the serine protease granzymes into cells targeted for destruction. Residing in cytotoxic cells, granzymes were originally anticipated to act both extracellularly and intracellularly. With the discovery that isolated granzymes induce apoptosis when combined with perforin, the broader functionality of the granzymes became unattractive. The purpose of this article is to describe observations indicating that granzymes possess non-cytotoxic activities that might include such diverse biologic effects as stimulation of pro-inflammatory cytokines, remodeling of extracellular matrices and inactivation of intracellular pathogens.
细胞毒性细胞颗粒分泌途径被视为通过一种过程消除肿瘤细胞和病毒感染细胞所不可或缺的，在此过程中，成孔蛋白穿孔素将丝氨酸蛋白酶颗粒酶递送至被靶向破坏的细胞中。颗粒酶存在于细胞毒性细胞中，最初预计其在细胞外和细胞内均发挥作用。随着发现分离出的颗粒酶与穿孔素结合时可诱导细胞凋亡，颗粒酶更广泛的功能就不再那么吸引人了。本文的目的是描述一些观察结果，这些结果表明颗粒酶具有非细胞毒性活性，可能包括刺激促炎细胞因子、重塑细胞外基质以及使细胞内病原体失活等多种生物学效应。
