Tsai S C, Heppner G H
Roche Diagnostic Systems, Branchburg, NJ 08876.
Cancer Immunol Immunother. 1994 Nov;39(5):291-8. doi: 10.1007/BF01519981.
We have previously shown that the immunoregulatory function of prolactin may play a role in the progression of the mouse mammary preneoplastic hyperplastic alveolar nodule (HAN) line C4 to carcinoma. In this study we investigated the direct effect of prolactin on lymphocytes isolated from normal and C4-HAN-bearing mice. In addition, we tested the effect of ovariectomy on prolactin/lymphocyte interaction to see whether, as has been reported in rats [Mukherjee P., Hymer W. C. (1992) Prog Neuroendocrinol Immunol 5: 108; Viselli S. M. et al. (1991) Endocrinology 129: 983], removal of estrogen would enhance the response to prolactin in mice. Proliferation of splenocytes, lymph node cells and HAN-infiltrating lymphocytes was stimulated by prolactin in a dose-responsive fashion. Ovariectomy did not alter this effect consistently. Cell-cycle analysis based on simultaneous staining of DNA and RNA revealed that prolactin-stimulated lymphocytes progress through all phases of the cell cycle whereas anti-prolactin antiserum inhibits this stimulation. Two-color flow-cytometric analysis revealed the time-dependent induction of interleukin-2 (IL-2) receptor expression on both CD4+ and CD8+ cells by prolactin. Prolactin-treated lymphocytes also produced low yet detectable levels of bioactive IL-2 in a dose- and time-dependent fashion. Prolactin enhanced lymphocyte responsiveness to mitogens and showed a marked synergism at suboptimal concentrations. Pretreatment of splenocytes from HAN bearers with a high concentration of prolactin slightly enhanced natural killer (NK) activity; anti-prolactin antiserum reduced the NK lytic activity of poly(I).poly(C)-activated splenocytes from HAN-bearing mice. Our results provide direct experimental evidence for the stimulatory effect of prolactin on lymphocyte function and IL-2-mediated lymphocyte proliferation and suggest a mechanism linking the endocrine system to immunomediated enhancement of HAN progression.
我们之前已经表明，催乳素的免疫调节功能可能在小鼠乳腺肿瘤前增生性肺泡结节（HAN）C4系发展为癌的过程中发挥作用。在本研究中，我们调查了催乳素对从正常小鼠和携带C4-HAN的小鼠中分离出的淋巴细胞的直接作用。此外，我们测试了卵巢切除术对催乳素/淋巴细胞相互作用的影响，以了解正如在大鼠中所报道的那样[穆克吉P.，海默W.C.（1992年）《神经内分泌免疫进展》5：108；维塞利S.M.等人（1991年）《内分泌学》129：983]，去除雌激素是否会增强小鼠对催乳素的反应。催乳素以剂量反应方式刺激脾细胞、淋巴结细胞和HAN浸润淋巴细胞的增殖。卵巢切除术并没有始终如一地改变这种作用。基于DNA和RNA同时染色的细胞周期分析表明，催乳素刺激的淋巴细胞经历细胞周期的所有阶段，而抗催乳素抗血清抑制这种刺激。双色流式细胞术分析显示，催乳素对CD4 +和CD8 +细胞上白细胞介素-2（IL-2）受体表达的诱导具有时间依赖性。经催乳素处理的淋巴细胞也以剂量和时间依赖性方式产生低但可检测水平的生物活性IL-2。催乳素增强了淋巴细胞对有丝分裂原的反应性，并在次优浓度下表现出明显的协同作用。用高浓度催乳素预处理HAN携带者的脾细胞可略微增强自然杀伤（NK）活性；抗催乳素抗血清降低了来自携带HAN小鼠的经聚肌苷酸-聚胞苷酸（poly(I).poly(C)）激活的脾细胞的NK裂解活性。我们的结果为催乳素对淋巴细胞功能和IL-2介导的淋巴细胞增殖具有刺激作用提供了直接的实验证据，并提出了一种将内分泌系统与免疫介导的HAN进展增强联系起来的机制。
