McConkey D J, Chow S C, Orrenius S, Jondal M
Department of Toxicology, Karolinska Institutet, Stockholm, Sweden.
FASEB J. 1990 Jun;4(9):2661-4. doi: 10.1096/fasebj.4.9.2347464.
In previous work we showed that programmed cell death (PCD) in thymocytes is mediated by a sustained increase in cytosolic Ca2+ concentration, resulting in the activation of an endogenous endonuclease, DNA fragmentation, and cell death. In this study we investigated the roles of Ca2+ and DNA fragmentation in target cell killing by natural killer (NK) cells. The effector cells induced a rapid, sustained increase in cytosolic Ca2+ concentration in Jurkat target cells. Buffering the target cell cytosolic Ca2+ with the Ca2(+)-selective dye, quin-2, prevented target cell killing. Extensive DNA fragmentation was associated with killing in every target tested, and this response was also blocked by quin-2. The endonuclease inhibitor, aurintricarboxylic acid, inhibited both DNA fragmentation and killing without influencing the Ca2+ increase in target cells. Thus, it is concluded that NK cell killing depends on a Ca2+ increase and appears to involve endogenous endonuclease activation in target cells.
在先前的研究中，我们发现胸腺细胞中的程序性细胞死亡（PCD）是由胞质Ca2+浓度持续升高介导的，导致内源性核酸内切酶激活、DNA片段化和细胞死亡。在本研究中，我们研究了Ca2+和DNA片段化在自然杀伤（NK）细胞杀伤靶细胞中的作用。效应细胞可诱导Jurkat靶细胞胞质Ca2+浓度迅速、持续升高。用Ca2+选择性染料喹啉-2缓冲靶细胞胞质Ca2+可阻止靶细胞被杀伤。在每个测试的靶细胞中，广泛的DNA片段化都与杀伤相关，并且这种反应也被喹啉-2阻断。核酸内切酶抑制剂金精三羧酸可抑制DNA片段化和杀伤，而不影响靶细胞中Ca2+的升高。因此，可以得出结论，NK细胞杀伤依赖于Ca2+的升高，并且似乎涉及靶细胞内源性核酸内切酶的激活。
