Malavé I, Rodriguez J, Araujo Z, Rojas I
Centro de Medicina Experimental, Instituto Venezolano de Investigaciones Cientificas, Caracas, Venezuela.
Immunopharmacology. 1990 Jul-Aug;20(1):1-10. doi: 10.1016/0162-3109(90)90002-v.
To study the effect of Zn on the proliferative response of normal human lymphocytes, ZnCl2 at a final concentration of 10(-4) M was added to cultures of peripheral blood mononuclear cells (PBMC) stimulated with concanavalin A (Con A) and to autologous mixed lymphocyte cultures of responder T lymphocytes and irradiated autologous non-T cells. Addition of Zn increased by about 50% the synthesis of DNA in cultures stimulated with either 10 or 20 micrograms/ml of Con A and markedly enhanced the autologous mixed lymphocyte reaction, which increased about 5-fold in the presence of Zn. In a narrow dose range, Zn induced per se the incorporation of [3H]thymidine by PBMC, with maximal effects in cultures stimulated with 10(-4) M ZnCl2. The percentage of cells expressing receptors for IL-2 and transferrin as assessed by immunofluorescence with the monoclonal antibodies (mAb) anti-Tac and OKT9, respectively, significantly increased when PBMC were stimulated with 10(-4) M ZnCl2 alone. Maximal [3H]thymidine incorporation and maximal percentage of cells bearing those activation markers were observed on day 6 of culture. Thus, the increase in the uptake of [3H]thymidine induced by Zn is not artifactual but due to progression in the cell cycle. Incubation with the mAb anti-Tac significantly inhibited the proliferative response to Zn, indicating that this requires binding of IL-2 to its receptor. However, addition of human recombinant IL-2 did not increase [3H]thymidine incorporation by PBMC cultured in the presence of ZnCl2.
为研究锌对正常人淋巴细胞增殖反应的影响，将终浓度为10⁻⁴M的氯化锌添加到用刀豆蛋白A（Con A）刺激的外周血单个核细胞（PBMC）培养物中，以及应答性T淋巴细胞与经照射的自体非T细胞的自体混合淋巴细胞培养物中。添加锌后，用10或20微克/毫升Con A刺激的培养物中DNA合成增加了约50%，并显著增强了自体混合淋巴细胞反应，在有锌存在的情况下该反应增加了约5倍。在较窄的剂量范围内，锌本身可诱导PBMC掺入[³H]胸腺嘧啶核苷，在10⁻⁴M氯化锌刺激的培养物中效果最佳。当PBMC单独用10⁻⁴M氯化锌刺激时，分别用抗Tac单克隆抗体（mAb）和OKT9通过免疫荧光评估的表达IL-2受体和转铁蛋白受体的细胞百分比显著增加。在培养的第6天观察到[³H]胸腺嘧啶核苷掺入量最大以及带有这些活化标记的细胞百分比最高。因此，锌诱导的[³H]胸腺嘧啶核苷摄取增加并非人为造成，而是由于细胞周期的进展。用抗Tac mAb孵育可显著抑制对锌的增殖反应，表明这需要IL-2与其受体结合。然而，添加人重组IL-2并未增加在氯化锌存在下培养的PBMC的[³H]胸腺嘧啶核苷掺入量。
