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结直肠癌患者外周血单个核细胞的增殖、白细胞介素-2产生及受体表达

Proliferation, interleukin-2 production and receptor expression in peripheral blood mononuclear cells from colorectal cancer patients.

作者信息

Chang K J, Wang S M, Lee C S, Hsieh K H, Chen K M

机构信息

Department of Surgery, College of Medicine, National Taiwan University, Taipei, R.O.C.

出版信息

J Formos Med Assoc. 1990 Mar;89(3):205-13.

PMID:1974593
Abstract

Peripheral blood mononuclear cells (PBMC) were cultured with phytohemagglutinin (PHA) in 46 colorectal cancer patients and 27 normal controls. By collectively comparing the cancer patients with the normal controls, the cancer patients had: (1) decreased interleukin-2 (IL-2) secretion, (2) fewer interleukin-2 receptor (IL-2R) expression on cell surface, and (3) less 3H thymidine incorporation. The ability of the phorbol ester, phorbol 12-myristate 13-acetate (PMA), and the calcium ionophore, A23187, in co-stimulation with PHA, to enhance the IL-2 secretion, IL-2R expression and 3H thymidine incorporation were studied in the PBMC of colorectal cancer patients. By adding A23187 into the PHA-stimulated PBMC from colorectal cancer patients, IL-2 production and IL-2R expression were increased up to levels equal to that obtained in PHA-stimulated PBMC from normal controls. Whereas there was no significant increase in proliferative response. However, PMA has no effect on all three parameters. A23187 is known to be effective in elevating cytosolic free Ca2+ and PMA is regarded as an activator of protein kinase C. Therefore, we may conclude that the impairment of IL-2 production and IL-2R expression in PHA-stimulated cultures is mainly due to failure of the free Ca2+ release which can be repaired by A23187. While protein kinase C activation may not be impaired since its deficit in IL-2 production and IL-2R expression can not be corrected by PMA.

摘要

对46例结直肠癌患者和27名正常对照者的外周血单个核细胞(PBMC)进行植物血凝素(PHA)培养。通过将癌症患者与正常对照者进行总体比较,发现癌症患者存在:(1)白细胞介素-2(IL-2)分泌减少;(2)细胞表面白细胞介素-2受体(IL-2R)表达减少;(3)3H-胸腺嘧啶核苷掺入减少。研究了佛波酯、佛波醇12-肉豆蔻酸酯13-乙酸酯(PMA)和钙离子载体A23187与PHA共同刺激对结直肠癌患者PBMC中IL-2分泌、IL-2R表达和3H-胸腺嘧啶核苷掺入的增强作用。在来自结直肠癌患者的PHA刺激的PBMC中加入A23187后,IL-2产生和IL-2R表达增加至与来自正常对照者的PHA刺激的PBMC所获得的水平相当。而增殖反应没有显著增加。然而,PMA对所有这三个参数均无影响。已知A23187可有效升高胞质游离Ca2+,而PMA被认为是蛋白激酶C的激活剂。因此,我们可以得出结论,PHA刺激培养物中IL-2产生和IL-2R表达的损害主要是由于游离Ca2+释放失败,而A23187可以修复这种失败。而蛋白激酶C激活可能未受损,因为其在IL-2产生和IL-2R表达方面的缺陷不能被PMA纠正。

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