Carolan E J, Casale T B
Department of Internal Medicine, VA Medical Center, Iowa City, IA.
J Immunol. 1990 Oct 15;145(8):2561-5.
Multiple molecular species of platelet activating factor (PAF) are produced as a result of inflammatory processes. PAF-induced neutrophil migration across endothelium is intrinsic to inflammatory responses. We therefore compared the ability of three naturally occurring PAF species (C16:0, C18:0, and C18:1), which only varied at carbon 1, to induce 51Cr-labeled human neutrophil migration across a naked 3-microns pore filter and human umbilical vein endothelial (HUVE) monolayers cultured on these filters. Time-course experiments indicated that all species of PAF tested induced significant neutrophil migration between 15 and 45 min. PAF-induced neutrophil migration through both filters alone and HUVE monolayers occurred at lower doses with C16:0 PAF. The rank order of chemotactic potency for the PAF species was C16:0 greater than C18:0 greater than C18:1 with both filters and endothelium coated filters as barriers. Intrinsic differences in the potency of these PAF molecular species to induce neutrophil chemotaxis were greater when HUVE cells were the barriers vs when filters alone were the barriers. Regardless of the molecular species used, at optimal PAF doses the degree of neutrophil migration through HUVE cells was often greater than that through filters alone. The specific PAF antagonist WEB 2086 inhibited neutrophil migration induced by all three PAF species equally. WEB 2086 pretreatment of the neutrophil or WEB 2086 coincubation with PAF, but not WEB 2086 pretreatment of the HUVE cell monolayers, significantly inhibited (65 to 80%) neutrophil migration. We conclude that the degree of PAF-induced neutrophil migration is dependent upon the molecular species of PAF. Moreover, the barrier through which the neutrophil must migrate appears to be important in influencing the overall chemotactic response to the various PAF species.
炎症过程会产生多种血小板活化因子（PAF）分子种类。PAF诱导的中性粒细胞跨内皮迁移是炎症反应的固有特征。因此，我们比较了三种仅在碳1位置有所不同的天然存在的PAF种类（C16:0、C18:0和C18:1）诱导51Cr标记的人类中性粒细胞穿过裸3微米孔径滤膜以及在这些滤膜上培养的人脐静脉内皮（HUVE）单层细胞的能力。时间进程实验表明，所有测试的PAF种类在15至45分钟之间均诱导了显著的中性粒细胞迁移。单独通过两种滤膜以及通过HUVE单层细胞时，C16:0 PAF以较低剂量诱导PAF诱导的中性粒细胞迁移。以两种滤膜和内皮细胞包被的滤膜作为屏障时，PAF种类的趋化效力排序为C16:0大于C18:0大于C18:1。当以HUVE细胞作为屏障时，这些PAF分子种类诱导中性粒细胞趋化的效力内在差异比仅以滤膜作为屏障时更大。无论使用哪种分子种类，在最佳PAF剂量下，中性粒细胞通过HUVE细胞的迁移程度通常大于单独通过滤膜的迁移程度。特异性PAF拮抗剂WEB 2086同等程度地抑制了所有三种PAF种类诱导的中性粒细胞迁移。对中性粒细胞进行WEB 2086预处理或使WEB 2086与PAF共同孵育，但不对HUVE细胞单层进行WEB 2086预处理，可显著抑制（65%至80%）中性粒细胞迁移。我们得出结论，PAF诱导的中性粒细胞迁移程度取决于PAF的分子种类。此外，中性粒细胞必须迁移通过的屏障似乎在影响对各种PAF种类的总体趋化反应中很重要。
