Enhancement of DNA synthesis and cAMP content of mouse thymocytes by mediator(s) derived from adherent cells.
Enhancement of DNA synthesis and cAMP content of mouse thymocytes by mediator(s) derived from adherent cells.
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通过贴壁细胞衍生的介质增强小鼠胸腺细胞的 DNA 合成和 cAMP 含量。
作者：
J. Oppenheim;A. Shneyour;A. I. Kook
粘附的小鼠腹腔渗出细胞或人单核细胞的上清液被用作淋巴细胞活化因子（LAF）的来源。发现LAF增强有丝分裂原如PHA和Con A对小鼠胸腺细胞DNA合成的影响。然而，LAF也能够减少胸腺细胞对Con A的强烈反应。因此，LAF通常比ConA更能增强PHA对BALB/c胸腺细胞DNA合成的影响。胸腺细胞的Con A与PHA反应的比率的这种变化表明，LAF可以作为胸腺细胞DNA合成的调节剂。此外，在存在LAF的情况下，同种异体胸腺细胞具有双向混合胸腺细胞反应的能力。暴露于LAF不仅提高了亲本胸腺细胞作为应答细胞的能力，而且还导致F1胸腺细胞的刺激活性增加，推测是通过促进刺激细胞的分化。通过研究LAF对胸腺细胞cAMP含量的影响，进一步研究了LAF影响分化的这些迹象。LAF刺激胸腺细胞膜的细胞内cAMP和腺苷酸环化酶活性的显着立即但短暂的升高。相反，促分裂剂本身不能提高或影响LAF对胸腺细胞内cAMP含量的影响。此外，LAF对有丝分裂原诱导的胸腺细胞DNA合成的增强作用有时被外源性cGMP、卡巴胆碱或咪唑增强。这些结果表明，LAF，通过其刺激cAMP水平在胸腺细胞中，可以反过来促进胸腺细胞充分分化，成为有能力的增殖反应有丝分裂原。
Supernatants of adherent mouse peritoneal exudate cells or human mononuclear cells were used as the source of lymphocyte activation factor (LAF). LAF was found to potentiate the effect of mitogens such as PHA and Con A on DNA synthesis by mouse thymocytes. However, LAF also was capable of reducing vigorous thymosyte reactions to Con A. Thus, LAF usually enhanced the effect of PHA on DNA synthesis by BALB/c thymocytes to a relatively greater degree than that of Con A. This change in the ratio of Con A to PHA response of thymocytes suggests that LAF can serve as a regulator of thymocyte DNA synthesis. Moreover, in the presence of LAF, allogeneic thymocytes developed the ability to have bidirectional mixed thymocyte reactions. Exposure to LAF not only improved the ability of parental thymocytes to act as responder cells, but, in addition, led to increased stimulatory activity of F1 thymocytes, presumably by promoting the differentiation of stimulator cells. These indications that LAF affected differentiation were investigated further by studying its effect on the cAMP content of thymocytes. LAF stimulated significant immediate but transient elevations of intracellular cAMP and adenylate cyclase activity in thymocyte membranes. In contrast, the mitogens themselves failed to elevate or to influence the effect of LAF on the content of intracellular cAMP of thymocytes. Furthermore, the potentiating effect of LAF on mitogen-induced thymocyte DNA synthesis at times was enhanced by exogenous cGMP, carbachol, or imidazole. These findings suggest that LAF, through its stimulation of cAMP levels in thymocytes may in turn promote thymocytes to differentiate sufficiently to become competent to proliferative in response to mitogens.