Strnad C F, Lin W Q, Carchman R A
Department of Pharmacology and Toxicology, Virginia Commonwealth University, Medical College of Virginia, Richmond 23298.
Immunology. 1989 Apr;66(4):539-45.
The B oligomer of pertussis toxin serves as a weak mitogen in the T lymphocyte, an effect which is associated with an early rise in cytosolic free calcium concentrations, as monitored by Fura-2 fluorescence. Upon co-administration of phorbol dibutyrate, a phorbol ester tumour promotor which activates protein kinase C, pertussis toxin-induced proliferation was synergistically enhanced, as measured by the increased uptake of [3H]thymidine, into cellular DNA. Although phorbol ester co-administration has often been associated with an inhibition of Ca2+-mobilizing pathways, phorbol dibutyrate pretreatment had no inhibitory effect on the pertussis toxin-induced calcium flux and may actually have enhanced this response slightly. Flow cytometric analysis of cell populations expanded by the combined regimen did not provide evidence for the preferential expansion of cells bearing either CD4 or CD8, the T-cell determinants representative of the helper-inducer and cytotoxic-suppressor subsets, respectively. Pertussis toxin and phorbol dibutyrate appear, therefore, to elicit polyclonal stimulation, rather than the selective activation of a given lymphocyte subset. Expression of the transferrin receptor, a marker for nutrient uptake, and CD25, the Tac component of the interleukin-2 (IL-2) receptor, was, however, synergistically enhanced in cells activated by the co-treatment procedure.
百日咳毒素的B寡聚体在T淋巴细胞中作为一种弱有丝分裂原，通过Fura-2荧光监测，这种作用与胞质游离钙浓度的早期升高有关。当同时给予佛波酯二丁酸酯（一种激活蛋白激酶C的佛波酯肿瘤促进剂）时，通过[3H]胸腺嘧啶核苷摄取到细胞DNA中的增加来衡量，百日咳毒素诱导的增殖被协同增强。尽管佛波酯的共同给药通常与Ca2+动员途径的抑制有关，但佛波酯二丁酸酯预处理对百日咳毒素诱导的钙通量没有抑制作用，实际上可能还略微增强了这种反应。对通过联合方案扩增的细胞群体进行流式细胞术分析，没有提供证据表明携带CD4或CD8的细胞优先扩增，CD4和CD8分别是辅助诱导和细胞毒性抑制亚群的T细胞决定簇。因此，百日咳毒素和佛波酯二丁酸酯似乎引发多克隆刺激，而不是特定淋巴细胞亚群的选择性激活。然而，转铁蛋白受体（一种营养摄取标记物）和CD25（白细胞介素-2（IL-2）受体的Tac成分）的表达在通过联合处理程序激活的细胞中被协同增强。
