Regner Matthias, Müllbacher Arno
Molecular Immunology and Immunopathology, John Curtin School of Medical Research, Australian National University, Canberra, ACT, Australia.
Immunol Cell Biol. 2004 Apr;82(2):161-9. doi: 10.1046/j.0818-9641.2004.01225.x.
Granzymes (gzm) are major components of the granules of cytolytic lymphocytes, natural killer and cytotoxic T cells. Their generally accepted mode of action consists of their directed secretion towards a virus-infected or neoplastic target cell and perforin-dependent delivery to the target cell cytosol, where they engage in various actions resulting in target cell apoptosis. Here, based on observations of infection of gzmAxB(-/-) mice with ectromelia virus, mousepox, we propose an additional--and distinct--function for gzmA and B. In this model, gzm constitute one of the first lines of defence of immune cells against virus infection of immune cells themselves. Accordingly, endogenous gzm interfere with viral replication in cytolytic lymphocytes either directly, as a result of their proteolytic activity, leading to destruction of viral proteins, or indirectly, via: (i) processes akin to the caspase cascade when acting as effector molecules in the induction of target cell apoptosis; or (ii) their capacity to induce early inflammatory mediators. We discuss the predictions of the model in the light of available data.
颗粒酶（gzm）是溶细胞性淋巴细胞、自然杀伤细胞和细胞毒性T细胞颗粒的主要成分。它们通常被认可的作用方式包括定向分泌至病毒感染或肿瘤靶细胞，并通过穿孔素依赖的方式递送至靶细胞胞质溶胶，在那里它们参与各种导致靶细胞凋亡的作用。在此，基于对gzmAxB（-/-）小鼠感染埃可病毒（鼠痘）的观察，我们提出gzmA和B具有另外一种独特功能。在这个模型中，gzm构成免疫细胞抵御免疫细胞自身病毒感染的第一道防线之一。因此，内源性gzm通过其蛋白水解活性直接干扰溶细胞性淋巴细胞中的病毒复制，导致病毒蛋白的破坏，或者通过以下方式间接干扰：（i）在诱导靶细胞凋亡时作为效应分子发挥作用时类似于半胱天冬酶级联反应的过程；或（ii）它们诱导早期炎症介质的能力。我们根据现有数据讨论该模型的预测结果。
