Gupta A, Hruska K A, Wedner H J
Renal Division, Jewish Hospital of St. Louis, Washington University, MO 63110.
Biochem Biophys Res Commun. 1990 Aug 16;170(3):1035-43. doi: 10.1016/0006-291x(90)90496-a.
Thymic-like lymphomas are very sensitive to killing by phytohemagglutinin. To investigate the mechanism of cytotoxicity, we studied the effect of PHA on cytosolic calcium [( Ca2+]i) and cAMP in the S49 mouse lymphoma cell line. PHA produced a slow continuing rise in [Ca2+]i. Estimation of cell number by Coulter counting showed that PHA induced rapid lysis of S49 cells in a dose-dependent manner. Nicardipine (10(-5) M) did not prevent PHA induced cell lysis or [Ca2+]i increase. Also ionomycin (10(-7) M) did not induce cell lysis. The data suggest that PHA induced increase in [Ca2+]i is the result rather than the cause of cell lysis. Elevated intracellular cAMP has an antiproliferative effect on S49 cells. PHA had no effect on cAMP levels in S49 cells. Also S49 cyc- clone which is deficient in Gs was susceptible to killing by PHA. These results suggest that the cytotoxic effect of PHA on S49 cells is rapid, but is not mediated by cAMP generation or an increase in [Ca2+]i, and other mechanisms should be investigated.
胸腺样淋巴瘤对植物血凝素介导的杀伤作用非常敏感。为了研究其细胞毒性机制,我们研究了植物血凝素(PHA)对S49小鼠淋巴瘤细胞系胞质钙浓度[Ca2+]i和环磷酸腺苷(cAMP)的影响。PHA使[Ca2+]i持续缓慢升高。通过库尔特计数法估算细胞数量显示,PHA以剂量依赖的方式诱导S49细胞快速裂解。尼卡地平(10(-5) M)不能阻止PHA诱导的细胞裂解或[Ca2+]i升高。同样,离子霉素(10(-7) M)也不能诱导细胞裂解。数据表明,PHA诱导的[Ca2+]i升高是细胞裂解的结果而非原因。细胞内cAMP升高对S49细胞具有抗增殖作用。PHA对S49细胞的cAMP水平没有影响。此外,缺乏Gs的S49 cyc-克隆对PHA介导的杀伤作用敏感。这些结果表明,PHA对S49细胞的细胞毒性作用迅速,但不是由cAMP生成或[Ca2+]i升高介导的,应研究其他机制。