Casale T B, Abbas M K, Carolan E J
Department of Internal Medicine, VA Medical Center, Iowa City, Iowa.
Am J Respir Cell Mol Biol. 1992 Jul;7(1):112-7. doi: 10.1165/ajrcmb/7.1.112.
Stimulated neutrophil migration across lung endothelial and epithelial barriers is important in lung inflammatory processes. To better understand the interaction between chemoattractants, neutrophils, and endothelium and epithelium, we compared the ability of leukotriene B4 (LTB4), formylmethionylleucylphenylalanine (FMLP), and platelet-activating factor (PAF) to induce human neutrophil migration across 3-microns-pore filters alone and human umbilical vein endothelial (HUVE) cells and two different epithelial cell types, Madin-Darby canine kidney (MDCK) cells and human lung A549 cells, cultured in monolayers on these filters. LTB4, FMLP, and PAF induced neutrophil migration through naked filters, endothelial cells, and epithelial cells in a dose-related fashion. At optimal chemoattractant doses, LTB4, FMLP, and PAF induced relatively equivalent neutrophil migration through filters and endothelial and epithelial monolayers. However, the doses at which optimal neutrophil migration was observed to occur as well as the degree of neutrophil migration through the three barriers varied depending upon the chemoattractant. Based on dose-response experiments, the relative rank order of potency for the three chemoattractants was: LTB4 = FMLP greater than PAF for filter alone barrier; LTB4 greater than FMLP greater than PAF for HUVE cell barrier; and FMLP greater than LTB4 greater than PAF for MDCK and A549 epithelial cell barriers. Our data suggest that neutrophil chemotactic and subsequent lung inflammatory responses are interrelatedly influenced by both the quantity and type of chemoattractant present and the barrier through which the neutrophil must migrate.
在肺部炎症过程中，受刺激的中性粒细胞穿越肺内皮和上皮屏障的迁移至关重要。为了更好地理解趋化因子、中性粒细胞与内皮细胞和上皮细胞之间的相互作用，我们比较了白三烯B4（LTB4）、甲酰甲硫氨酰亮氨酰苯丙氨酸（FMLP）和血小板活化因子（PAF）单独诱导人中性粒细胞穿越3微米孔径滤膜以及在这些滤膜上单层培养的人脐静脉内皮（HUVE）细胞和两种不同上皮细胞类型（犬肾Madin-Darby细胞（MDCK）和人肺A549细胞）的能力。LTB4、FMLP和PAF以剂量相关的方式诱导中性粒细胞穿越裸露滤膜、内皮细胞和上皮细胞。在最佳趋化因子剂量下，LTB4、FMLP和PAF诱导中性粒细胞穿越滤膜以及内皮和上皮单层的迁移相对相当。然而，观察到最佳中性粒细胞迁移发生时的剂量以及中性粒细胞穿越这三种屏障的程度因趋化因子而异。基于剂量反应实验，三种趋化因子的相对效力排序为：对于单独的滤膜屏障，LTB4 = FMLP＞PAF；对于HUVE细胞屏障，LTB4＞FMLP＞PAF；对于MDCK和A549上皮细胞屏障，FMLP＞LTB4＞PAF。我们的数据表明，中性粒细胞的趋化作用以及随后的肺部炎症反应受到趋化因子的数量和类型以及中性粒细胞必须穿越的屏障的相互关联影响。
