Activation of NK cell cytotoxicity
Activation of NK cell cytotoxicity
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DOI：
10.1016/j.molimm.2004.07.034
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发表时间：
2005-02-01
影响因子：
3.6
通讯作者：
Hayakawa, Y
中科院分区：
文献类型：
--
作者：
Smyth, MJ;Cretney, E;Hayakawa, Y
自然杀伤（NK）细胞是防御应激、微生物感染或恶性细胞所必需的先天效应淋巴细胞。NK细胞通过两种主要机制中的任一种杀死靶细胞，这两种机制需要NK细胞和靶细胞之间的直接接触。在第一种途径中，细胞质颗粒毒素，主要是一种膜破坏蛋白，称为穿孔素，和一个家族的结构相关的丝氨酸C，蛋白酶（颗粒酶）与各种底物特异性，分泌的胞吐作用，并共同诱导靶细胞的凋亡。颗粒胞吐途径有效地激活细胞死亡机制，该机制通过激活凋亡半胱氨酸蛋白酶（caspase）来起作用，但也可以在不存在激活的caspase的情况下引起细胞死亡。第二种途径涉及靶细胞上的死亡受体（例如Fas/CD 95）与其同源配体（例如NK细胞上的FasL）的结合，导致经典的半胱天冬酶依赖性细胞凋亡。这些途径在许多疾病的病理生理学中的比较作用正在通过对缺乏这些分子的基因靶向小鼠和具有影响这些途径的基因突变的人类的分析来剖析。我们现在还了解到，NK细胞的效应功能是由涉及特定NK细胞受体及其同源配体的相互作用控制的，无论是在靶细胞上，还是在免疫系统的其他细胞上。本文将讨论NK细胞的细胞毒性和受体/配体的相互作用，控制这些过程的功能的重要性。(C)2004爱思唯尔有限公司保留所有权利。
Natural killer (NK) cells are innate effector lymphocytes necessary for defence against stressed, microbe-infected, or malignant cells. NK cells kill target cells by either of two major mechanisms that require direct contact between NK cells and target cells. In the first pathway, cytoplasmic granule toxins, predominantly a membrane-disrupting protein known as perforin, and a family of structurally related serine C, proteases (granzymes) with various substrate specificities, are secreted by exocytosis and together induce apoptosis of the target cell. The granule-exocytosis pathway potently activates cell-death mechanisms that operate through the activation of apoptotic cysteine proteases (caspases), but can also cause cell death in the absence of activated caspases. The second pathway involves the engagement of death receptors (e.g. Fas/CD95) on target cells by their cognate ligands (e.g. FasL on NK cells, resulting in classical caspase-dependent apoptosis. The comparative role of these pathways in the pathophysiology of many diseases is being dissected by analyses of gene-targeted mice that lack these molecules, and humans who have genetic mutations affecting these pathways. We are also now learning that the effector function of NK cells is controlled by interactions involving specific NK cell receptors and their cognate ligands, either on target cells, or other cells of the immune system. This review will discuss the functional importance of NK cell cytotoxicity and the receptor/ligand interactions that control these processes. (C) 2004 Elsevier Ltd. All rights reserved.