Beusenberg F D, Hoogsteden H C, Bonta I L, van Amsterdam J G
Department of Pharmacology, Faculty of Medicine, Erasmus University Rotterdam, The Netherlands.
Life Sci. 1994;54(17):1269-74. doi: 10.1016/0024-3205(94)00854-x.
The effect of the phosphodiesterase inhibitor isobutyl-methylxanthine (IBMX), salbutamol and sodium nitroprusside was evaluated regarding PGE2 and LTB4 release and cAMP and cGMP level in human alveolar macrophages obtained from controls and COPD patients. Basal levels per five million control- respectively COPD alveolar macrophages: cAMP 1.2 and 1.0 pmole; cGMP 8.4 and 9.1 fmole; PGE2 120 and 63 pg and LTB4 19.2 and 14.8 pg. In both populations IBMX increased cAMP level by 55-93% and salbutamol+IBMX by 285-252%. Except for the 61% rise in LTB4 release by salbutamol+IBMX the drugs hardly affected PGE2 and LTB4 release from control macrophages. In COPD alveolar macrophages, however, IBMX and IBMX+salbutamol largely reduced PGE2 release (63 vs 11 pg per 10(6) cells) but less efficiently increased LTB4. In both macrophage populations sodium nitroprusside (SNP) substantially increased (3-4 fold) cGMP level but did not affect eicosanoid production. Present results indicate that drugs which enhance cAMP level decrease PGE2 release from COPD macrophages and stimulate the release of LTB4 a chemotactic mediator involved in bronchial inflammatory reactions.
就从对照组和慢性阻塞性肺疾病（COPD）患者获取的人肺泡巨噬细胞中前列腺素E2（PGE2）和白三烯B4（LTB4）的释放以及环磷酸腺苷（cAMP）和环磷酸鸟苷（cGMP）水平，对磷酸二酯酶抑制剂异丁基甲基黄嘌呤（IBMX）、沙丁胺醇和硝普钠的作用进行了评估。每五百万个对照和COPD肺泡巨噬细胞的基础水平分别为：cAMP 1.2皮摩尔和1.0皮摩尔；cGMP 8.4飞摩尔和9.1飞摩尔；PGE2 120皮克和63皮克；LTB4 19.2皮克和14.8皮克。在这两组人群中，IBMX使cAMP水平升高了55% - 93%，沙丁胺醇 + IBMX使cAMP水平升高了285% - 252%。除了沙丁胺醇 + IBMX使LTB4释放增加61%外，这些药物几乎不影响对照巨噬细胞中PGE2和LTB4的释放。然而，在COPD肺泡巨噬细胞中，IBMX和IBMX + 沙丁胺醇大幅降低了PGE2的释放（每10⁶个细胞从63皮克降至11皮克），但增加LTB4的效率较低。在这两组巨噬细胞中，硝普钠（SNP）使cGMP水平大幅升高（3 - 4倍），但不影响类花生酸的产生。目前的结果表明，提高cAMP水平的药物可减少COPD巨噬细胞中PGE2的释放，并刺激LTB4的释放，LTB4是一种参与支气管炎症反应的趋化介质。
