Carolan E J, Mower D A, Casale T B
Department of Internal Medicine, University of Iowa College of Medicine, and Veterans Administration Medical Center, Iowa City, USA.
Am J Respir Cell Mol Biol. 1997 Dec;17(6):727-32. doi: 10.1165/ajrcmb.17.6.2745.
The mechanisms by which mediators and cytokines stimulate neutrophils to migrate across the lung epithelium are still unclear. We hypothesized that neutrophil transepithelial migration depends upon polarity of the epithelium. We therefore compared neutrophil migration through human lung Type II-like alveolar epithelial cell line (A549) monolayers grown on the upper versus lower surface of permeable filters to simulate apical-to-basal and basal-to-apical movement of neutrophils, respectively. The classic chemoattractants formyl-methionylleucylphenylalanine (FMLP), leukotriene B4 (LTB4), and interleukin-8 (IL-8) induced equivalent neutrophil transepithelial migration in the apical-to-basal and basal-to-apical directions. However, the degree of neutrophil transepithelial migration was significantly greater in the basal-to-apical direction in response to either IL-1beta or tumor necrosis factor-alpha (TNF-alpha). Enhanced TNF-alpha-induced neutrophil migration through A549 monolayers in the basal-to-apical direction occurred regardless of whether the TNF-alpha was above or below the filter/monolayer complex. Actinomycin D pretreatment of A549 monolayers had no effect on FMLP-induced neutrophil transepithelial migration, but markedly (about 75%) inhibited both TNF-alpha- and IL-1beta-induced neutrophil transepithelial migration, regardless of monolayer orientation. Thus, in contrast to classic chemoattractants, IL-1beta and TNF-alpha induced greater neutrophil transepithelial migration in a basal-to-apical direction, and this occurred independently of the cytokine location, but depended upon intact metabolic capacity of the A549 cells. These data suggest that the mechanisms important for neutrophil transepithelial migration in response to classic chemoattractants differ from those important for migration in response to inflammatory cytokines.
介质和细胞因子刺激中性粒细胞穿过肺上皮细胞迁移的机制仍不清楚。我们推测中性粒细胞跨上皮迁移取决于上皮细胞的极性。因此，我们比较了中性粒细胞通过生长在可渗透滤器上表面和下表面的人II型肺泡上皮样细胞系（A549）单层的迁移情况，分别模拟中性粒细胞从顶端到基底和从基底到顶端的移动。经典趋化因子甲酰甲硫氨酰亮氨酰苯丙氨酸（FMLP）、白三烯B4（LTB4）和白细胞介素-8（IL-8）在从顶端到基底和从基底到顶端的方向上诱导等量的中性粒细胞跨上皮迁移。然而，响应IL-1β或肿瘤坏死因子-α（TNF-α）时，中性粒细胞跨上皮迁移的程度在从基底到顶端的方向上显著更高。无论TNF-α是在滤器/单层复合物之上还是之下，TNF-α诱导的中性粒细胞在从基底到顶端方向上通过A549单层的迁移都会增强。用放线菌素D预处理A549单层对FMLP诱导的中性粒细胞跨上皮迁移没有影响，但显著（约75%）抑制了TNF-α和IL-1β诱导的中性粒细胞跨上皮迁移，无论单层的方向如何。因此，与经典趋化因子不同，IL-1β和TNF-α在从基底到顶端的方向上诱导更大程度的中性粒细胞跨上皮迁移，并且这种迁移与细胞因子的位置无关，但取决于A549细胞完整的代谢能力。这些数据表明，对经典趋化因子作出反应时中性粒细胞跨上皮迁移的重要机制不同于对炎性细胞因子作出反应时迁移的重要机制。
