Casale T B, Erger R A, Little M M
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242-1009.
Am J Respir Cell Mol Biol. 1993 Jan;8(1):77-82. doi: 10.1165/ajrcmb/8.1.77.
Stimulated migration of eosinophils out of the bloodstream and into the lung is key in the development of tissue eosinophilia and inflammation in asthma. Platelet-activating factor (PAF) has been implicated as an important inflammatory mediator in asthma pathogenesis in part because of its chemotactic capacity. We therefore studied the ability of PAF to induce human peripheral blood eosinophil migration through naked filters and human umbilical vein endothelial cells (HUVECs) cultured on these filters. PAF induced eosinophil migration through both barriers in a time-dependent fashion, with maximal eosinophil migration occurring at 180 min. Significant eosinophil migration was observed at PAF concentration > or = 0.1 microM and was dose dependent up to 10.0 microM. No significant differences in eosinophil chemotactic responses were noted between naked filter and HUVEC barriers. The PAF receptor antagonist, WEB 2086, inhibited (> 85%) eosinophil transendothelial migration when co-incubated with PAF or when used as a pretreatment of either the eosinophils or HUVECs. However, WEB 2086 pretreatment of HUVECs did not inhibit PAF-induced neutrophil transendothelial migration, nor did it affect leukotriene B4-induced neutrophil or eosinophil transendothelial migration. Thus, the data indicate that the endothelial cell plays an important role in PAF-induced eosinophil inflammatory processes. Moreover, these data suggest that PAF's pathogenic role in asthma may in part be due to its ability to stimulate eosinophil migration across endothelial barriers and into the airways.
嗜酸性粒细胞从血液中迁移至肺部并受到刺激，这是哮喘中组织嗜酸性粒细胞增多和炎症发展的关键环节。血小板活化因子（PAF）被认为是哮喘发病机制中的一种重要炎症介质，部分原因在于其趋化能力。因此，我们研究了PAF诱导人外周血嗜酸性粒细胞通过裸滤膜以及在这些滤膜上培养的人脐静脉内皮细胞（HUVECs）进行迁移的能力。PAF以时间依赖性方式诱导嗜酸性粒细胞通过这两种屏障迁移，在180分钟时嗜酸性粒细胞迁移达到最大值。当PAF浓度≥0.1微摩尔时观察到显著的嗜酸性粒细胞迁移，且在高达10.0微摩尔时呈剂量依赖性。在裸滤膜和HUVEC屏障之间，未观察到嗜酸性粒细胞趋化反应的显著差异。PAF受体拮抗剂WEB 2086与PAF共同孵育时，或用作嗜酸性粒细胞或HUVECs的预处理时，可抑制（>85%）嗜酸性粒细胞跨内皮迁移。然而，对HUVECs进行WEB 2086预处理并不能抑制PAF诱导的中性粒细胞跨内皮迁移，也不影响白三烯B4诱导的中性粒细胞或嗜酸性粒细胞跨内皮迁移。因此，数据表明内皮细胞在PAF诱导的嗜酸性粒细胞炎症过程中起重要作用。此外，这些数据表明PAF在哮喘中的致病作用可能部分归因于其刺激嗜酸性粒细胞跨内皮屏障迁移至气道的能力。
