Fuse A, Sato T, Kuwata T
Int J Cancer. 1981 Jan 15;27(1):29-36. doi: 10.1002/ijc.2910270106.
Cholera toxin inhibits human natural cell-mediated cytotoxicity in a dose- and time-dependent manner. Pretreatment of lymphocytes with 10 ng/ml of cholera toxin for 2 h almost completely inhibited cytolysis. Interferon augmented human natural cell-mediated cytolysis, but when lymphocytes were pretreated with cholera toxin before interferon treatment, no enhancement of cytolysis occurred. Cholera toxin could inhibit the enhancement of cytolysis by interferon even when lymphocytes were treated with cholera toxin after 2 h interferon treatment. Cholera toxin subunit B which binds cell surface ganglioside galactosyl-N-acetylgalactosaminyl - [N-acetylneuraminyl] - galactosylglucosylceramide (GM1) without activating adenyl cyclase had no effect either on natural cytolysis or on the enhancement of natural cytolysis by interferon, suggesting that mere binding of cholera toxin to the cellular receptor was not enough to inhibit natural cell-mediated cytolysis. Cyclic adenosine 3',5'-monophosphate (cAMP) levels increased in cholera toxin-treated lymphocytes and the time course of cAMP accumulation was similar to that of cytotoxicity inhibition. Exogenous dibutyryl-cAMP (db-cAMP) and theophylline inhibited cytolysis, while exogenous dibutyryl cyclic guanosine 3',5'-phosphate (db-cGMP) enhanced cytolysis slightly, suggesting that the process of inhibition of human natural cell-mediated cytolysis was at least partly modulated by intracellular cyclic nucleotides.
霍乱毒素以剂量和时间依赖的方式抑制人类自然细胞介导的细胞毒性。用10 ng/ml霍乱毒素预处理淋巴细胞2小时几乎完全抑制细胞溶解。干扰素增强人类自然细胞介导的细胞溶解，但当淋巴细胞在干扰素处理前用霍乱毒素预处理时，细胞溶解没有增强。即使淋巴细胞在干扰素处理2小时后用霍乱毒素处理，霍乱毒素也能抑制干扰素对细胞溶解的增强作用。霍乱毒素亚基B可结合细胞表面神经节苷脂半乳糖基-N-乙酰半乳糖胺基-[N-乙酰神经氨酸基]-半乳糖基葡萄糖基神经酰胺（GM1），但不激活腺苷酸环化酶，对自然细胞溶解或干扰素增强自然细胞溶解均无影响，这表明霍乱毒素仅与细胞受体结合不足以抑制自然细胞介导的细胞毒性。霍乱毒素处理的淋巴细胞中3',5'-环磷酸腺苷（cAMP）水平升高，cAMP积累的时间进程与细胞毒性抑制的时间进程相似。外源性二丁酰-cAMP（db-cAMP）和茶碱抑制细胞溶解，而外源性二丁酰环鸟苷3',5'-磷酸（db-cGMP）略微增强细胞溶解，这表明人类自然细胞介导的细胞溶解抑制过程至少部分受细胞内环核苷酸调节。
