Bruynzeel P L, Koenderman L, Kok P T, Hameling M L, Verhagen J
Pharmacol Res Commun. 1986 Aug;18 Suppl:61-9. doi: 10.1016/0031-6989(86)90039-1.
Human eosinophils are capable of synthesizing almost exclusively the strongly spasmogenic compound LTC4 when stimulated with either the calcium ionophore A 23187 or opsonized zymosan (OZ). Although PAF-acether in concentrations ranging from 10 nM to 1 microM is hardly capable of inducing significant LTC4 synthesis itself, it significantly enhances the OZ-induced LTC4 formation at a concentration of 1 microM. However, at a concentration of 10 microM, PAF-acether itself is capable of inducing LTC4 formation comparable with that induced by OZ. PAF-acether, at a concentration of 10 microM (and not at a concentration of 1 microM) is also capable of inducing a luminol dependent chemiluminescent response by eosinophils. The PAF-acether antagonist BN 52021 at a concentration of 0.1 mM not only partially inhibited the PAF-acether induced LTC4 formation but also the OZ induced LTC4 formation. Since an equal inhibition is found the inhibitory mode of action of BN 52021 is most likely directed towards a common pathway. Taken together, these results suggest that eosinophils may be triggered by high locally reached concentrations of PAF-acether to release inflammatory and bronchoconstrictive mediators. This may be of importance for the pathogenesis of the allergen induced late phase asthmatic reaction.
当用钙离子载体A 23187或调理酵母聚糖（OZ）刺激时，人类嗜酸性粒细胞几乎只能合成强烈致痉挛化合物LTC4。虽然浓度范围为10 nM至1 microM的血小板活化因子（PAF - 乙醚）本身几乎不能诱导显著的LTC4合成，但在1 microM浓度下，它能显著增强OZ诱导的LTC4形成。然而，在10 microM浓度下，PAF - 乙醚本身能够诱导与OZ诱导相当的LTC4形成。浓度为10 microM（而非1 microM）的PAF - 乙醚也能够诱导嗜酸性粒细胞产生依赖鲁米诺的化学发光反应。浓度为0.1 mM的PAF - 乙醚拮抗剂BN 52021不仅部分抑制了PAF - 乙醚诱导的LTC4形成，还抑制了OZ诱导的LTC4形成。由于发现了同等程度的抑制作用，BN 52021的抑制作用模式很可能针对的是一条共同途径。综上所述，这些结果表明，嗜酸性粒细胞可能会被局部高浓度的PAF - 乙醚触发，从而释放炎症和支气管收缩介质。这可能对变应原诱导的迟发性哮喘反应的发病机制具有重要意义。
