摘要
利用选择性磷酸二酯酶抑制剂和激活剂,用半定量方法分析了人细胞制剂和组织的磷酸二酯酶同工酶谱。中性粒细胞、嗜酸性粒细胞和单核细胞只含有PDE IV。淋巴细胞、肺泡巨噬细胞和内皮细胞中均含有PDE IV和PDE III,此外,巨噬细胞中测定PDE I,内皮细胞中测定PDE II。这些基细胞特异性PDE同工酶谱似乎受到以下因素的影响:1)底物浓度;2)激酶依赖性磷酸化;3)调节合成速率。因此,PDE同工酶谱表现为动态模式,明显适应病理和环境条件。在平行功能研究中,单选择性(罗立普兰,PDE IV;比较了莫他松、PDE III、双选择性(扎达弗林)和非选择性(茶碱)PDE抑制剂。同工酶分析表明,PDE III和PDE IV必须被抑制才能完全抑制巨噬细胞释放肿瘤坏死因子- α (tnf - α)或淋巴细胞增殖(PDE III/IV细胞)。 In eosinophils (PDE IV cells) platelet-activating factor (PAF)-induced chemotaxis or C5a-stimulated degranulation are only weakly inhibited by rolipram alone. After addition of a beta 2-agonist, however, the efficacy of rolipram is enhanced due to concomitant influence of synthesis and breakdown of cyclic adenosine monophosphate (cAMP). Theophylline inhibits PDE isoenzyme activities and functions of inflammatory cells with similar potency, and exhibits higher functional efficacy as compared to rolipram.