Herlin T, Kragballe K
Int Arch Allergy Appl Immunol. 1983;72(1):1-5. doi: 10.1159/000234831.
Addition of IgG-sensitized human erythrocytes to peripheral blood monocytes elicit a transient increment in monocyte cAMP levels. This increase in cAMP was facilitated when monocytes were preincubated with the phosphodiesterase inhibitors, isobutylmethylxanthine (IBMX) and theophylline, and the adenylate cyclase agonists, isoproterenol and prostaglandin E1 (PGE1). Although these cAMP elevating agents were able to inhibit monocyte ADCC, the degree of inhibition could not be anticipated from the cAMP levels achieved by these drugs since theophylline inhibited monocyte ADCC in doses not elevating cAMP and PGE1, isoproterenol and IBMX were less effective inhibitors of monocyte ADCC than theophylline when comparing their effects on cAMP levels. Both PGE1-induced elevation of cAMP levels and the further increments of cAMP after addition of IgG-sensitized erythrocytes to PGE1-treated monocytes were significantly correlated to the inhibition of beta-glucuronidase release during ADCC. Theophylline in doses of 0.5 mM did not elevate basal levels of monocyte cAMP but facilitated the ADCC-induced cAMP increment concomitant with inhibition of monocyte ADCC and degranulation. Possibly, facilitation of cAMP increments during ADCC by an inhibitory feedback mechanism may be responsible for the inhibition caused by cAMP-elevating agents.
将IgG致敏的人红细胞添加到外周血单核细胞中会引起单核细胞cAMP水平短暂升高。当单核细胞与磷酸二酯酶抑制剂异丁基甲基黄嘌呤（IBMX）和茶碱以及腺苷酸环化酶激动剂异丙肾上腺素和前列腺素E1（PGE1）预孵育时，cAMP的这种升高会更明显。尽管这些cAMP升高剂能够抑制单核细胞的抗体依赖细胞介导的细胞毒性作用（ADCC），但无法从这些药物所达到的cAMP水平预测抑制程度，因为茶碱在不升高cAMP的剂量下就能抑制单核细胞ADCC，并且当比较它们对cAMP水平的影响时，PGE1、异丙肾上腺素和IBMX作为单核细胞ADCC的抑制剂比茶碱效果更差。PGE1诱导的cAMP水平升高以及将IgG致敏红细胞添加到PGE1处理的单核细胞后cAMP的进一步升高均与ADCC过程中β-葡萄糖醛酸酶释放的抑制显著相关。0.5 mM剂量的茶碱不会升高单核细胞cAMP的基础水平，但会促进ADCC诱导的cAMP升高，同时抑制单核细胞ADCC和脱颗粒。可能是通过抑制性反馈机制促进ADCC期间的cAMP升高导致了cAMP升高剂所引起的抑制作用。
