Marquardt D L, Walker L L
Department of Medicine, University of California San Diego Medical Center 92103.
J Immunol. 1989 Feb 15;142(4):1268-73.
Adenosine potentiates preformed mediator release from mouse bone marrow-derived mast cells stimulated with specific Ag or the calcium ionophore A23187. When these mast cells were cultured for 30 to 120 min with the phorbol ester PMA (10(-8) or 10(-7) M), protein kinase C activity was increased and Ag-stimulated beta-hexosaminidase release was modestly inhibited, whereas A23187-stimulated release was synergistically enhanced. However, in both cases, exogenous adenosine failed to augment beta-hexosaminidase release. Overnight PMA exposure produced a decrease in protein kinase C activity and a decrease in both Ag- and A23187-stimulated preformed mediator release, as well as a lack of responsiveness to adenosine. This hyporesponsiveness could be reversed by 24 h after washing the cells free of PMA. The generation of the arachidonic acid metabolite leukotriene C4 was not altered by mast cell PMA exposure. The ability of adenosine to increase intracellular cAMP concentrations was modestly blunted by high doses of PMA, and PMA abrogated the increase in intracellular free calcium levels usually observed in cells stimulated with Ag in the presence of 10(-5) M adenosine. PMA exposure induces a hyporesponsiveness to adenosine in mast cells, either by a direct effect on protein kinase C activity and/or by an effect on adenosine receptor expression or recycling.
腺苷可增强由特异性抗原或钙离子载体A23187刺激的小鼠骨髓来源肥大细胞中预先形成的介质释放。当这些肥大细胞用佛波酯PMA（10^(-8)或10^(-7) M）培养30至120分钟时，蛋白激酶C活性增加，抗原刺激的β-己糖胺酶释放受到适度抑制，而A23187刺激的释放则协同增强。然而，在这两种情况下，外源性腺苷均未能增加β-己糖胺酶的释放。过夜暴露于PMA会导致蛋白激酶C活性降低，抗原和A23187刺激的预先形成的介质释放均减少，以及对腺苷缺乏反应性。在将细胞洗涤去除PMA后24小时，这种低反应性可得到逆转。肥大细胞暴露于PMA不会改变花生四烯酸代谢产物白三烯C4的生成。高剂量的PMA会适度削弱腺苷增加细胞内cAMP浓度的能力，并且PMA消除了通常在存在10^(-5) M腺苷的情况下由抗原刺激的细胞中观察到的细胞内游离钙水平的升高。PMA暴露通过对蛋白激酶C活性的直接作用和/或对腺苷受体表达或循环的影响，诱导肥大细胞对腺苷产生低反应性。
