Whalen M M, Green C B
Department of Chemistry, Murray State University, KY 42071, USA.
Immunology. 1998 Mar;93(3):415-20. doi: 10.1046/j.1365-2567.1998.00411.x.
Natural killer (NK) cells are lymphocytes that are capable of destroying tumour cells and virally infected cells (cytolysis) without prior sensitization. When cAMP is artificially elevated in NK cells, it is a potent inhibitor of their cytolytic function. We investigated whether NK-cell cAMP levels are modulated in response to tumour target cells to determine the potential of cAMP as a physiological regulator of NK cytotoxic function. When NK cells are exposed to a range of lysis-sensitive (LS) tumour-target cells there is an increase in intracellular cAMP levels in the NK cells over a 60-min period. The peak increase in cAMP (200-400% above control) occurs at 30 min for all LS targets tested. There is no increase in NK-cell cAMP in response to lysis-resistant (LR) tumour-target cells. The cAMP elevation may be dependent on both LS-target-stimulated adenylyl cyclase (AC) activation and LS-target-stimulated phosphodiesterase (PDE) inhibition. When the NK cells are pretreated with the protein tyrosine kinase (PTK) inhibitor, genistein (30 micrograms/ml), the AC-activation component of the cAMP elevation is abolished. Thus, the AC-activation component appears to require PTK activation. When NK cells are pretreated with the protein kinase C (PKC) inhibitor, chelerythrine chloride (10 microM) the cAMP elevation in response to LS targets was not diminished. This indicates that neither the AC-activation component nor any PDE-inhibition component require PKC activation.
自然杀伤（NK）细胞是一种淋巴细胞，能够在无需预先致敏的情况下破坏肿瘤细胞和病毒感染细胞（细胞溶解）。当NK细胞中的环磷酸腺苷（cAMP）人工升高时，它是其细胞溶解功能的有效抑制剂。我们研究了NK细胞的cAMP水平是否会响应肿瘤靶细胞而受到调节，以确定cAMP作为NK细胞毒性功能生理调节剂的潜力。当NK细胞暴露于一系列对细胞溶解敏感（LS）的肿瘤靶细胞时，在60分钟内NK细胞内的cAMP水平会升高。对于所有测试的LS靶细胞，cAMP的峰值升高（比对照高200 - 400%）在30分钟时出现。NK细胞对细胞溶解抗性（LR）肿瘤靶细胞无cAMP升高反应。cAMP的升高可能既依赖于LS靶细胞刺激的腺苷酸环化酶（AC）激活，也依赖于LS靶细胞刺激的磷酸二酯酶（PDE）抑制。当用蛋白酪氨酸激酶（PTK）抑制剂染料木黄酮（30微克/毫升）预处理NK细胞时，cAMP升高的AC激活成分被消除。因此，AC激活成分似乎需要PTK激活。当用蛋白激酶C（PKC）抑制剂氯化白屈菜红碱（10微摩尔）预处理NK细胞时，对LS靶细胞的cAMP升高没有减弱。这表明AC激活成分和任何PDE抑制成分都不需要PKC激活。
