Whalen M M, Bankhurst A D
Department of Medicine, University of New Mexico School of Medicine, Albuquerque 87131.
Biochem J. 1990 Dec 1;272(2):327-31. doi: 10.1042/bj2720327.
Membranes from highly purified natural killer (NK) cells were ADP-ribosylated by treatment with cholera toxin (CTX). CTX resulted in a single band of specific 32P incorporation at Mr 43,600. CTX treatment of intact NK cells caused a 9-fold increase in cyclic AMP (cAMP) concentrations. Pretreatment of NK cells with CTX diminished their ability to lyse K562 tumour cells by up to 79%. Forskolin treatment elevated NK cell cAMP levels 8-fold and decreased lysis of K562 cells by up to 45%. Adrenaline and isoprenaline (isoproterenol) both inhibited lysis of K562 cells by approx. 35% and elevated cAMP by at least 2.5-fold, and their inhibition of lysis was reversed by propranolol. These data suggest that the stimulatory guanine-nucleotide-binding protein GS coupled to beta-adrenergic receptors is involved in transducing signals which inhibit NK cell lysis of tumour cells. CTX and forskolin also diminish the ability of NK cells to bind K562 cells (binding is necessary for lysis). This suggests that the NK-cell receptor(s) for the tumour cell may be altered as a consequence of cAMP-mediated events or by activation of GS.
用霍乱毒素（CTX）处理来自高度纯化的自然杀伤（NK）细胞的细胞膜，可使其发生ADP-核糖基化。CTX导致在分子量43,600处出现一条特异性32P掺入的条带。用CTX处理完整的NK细胞会使环磷酸腺苷（cAMP）浓度增加9倍。用CTX预处理NK细胞可使其裂解K562肿瘤细胞的能力降低多达79%。用福斯高林处理可使NK细胞的cAMP水平升高8倍，并使K562细胞的裂解减少多达45%。肾上腺素和异丙肾上腺素（异丙基去甲肾上腺素）均能使K562细胞的裂解受到约35%的抑制，并使cAMP升高至少2.5倍，它们对裂解的抑制作用可被普萘洛尔逆转。这些数据表明，与β-肾上腺素能受体偶联的刺激性鸟嘌呤核苷酸结合蛋白Gs参与了转导抑制NK细胞对肿瘤细胞裂解的信号。CTX和福斯高林还会降低NK细胞结合K562细胞的能力（结合是裂解所必需的）。这表明肿瘤细胞的NK细胞受体可能会因cAMP介导的事件或Gs的激活而发生改变。
