Liu L, Mul F P, Lutter R, Roos D, Knol E F
Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam.
Am J Respir Cell Mol Biol. 1996 Dec;15(6):771-80. doi: 10.1165/ajrcmb.15.6.8969272.
To study the mechanisms involved in the movement of neutrophils from the blood stream into the lung airways, we investigated human neutrophil transmigration across a monolayer of human airway epithelial cells, both in the apical-to-basolateral direction and in the more physiologic basolateral-to-apical direction. Migration of human neutrophils across monolayers of human airway epithelial H292 cell-line cells and primary bronchial epithelial cells occured most efficiently in the basolateral-to-apical direction, both after the addition of chemoattractants to resting epithelial cells and across interleukin-1beta (IL-1beta)-stimulated epithelial cells. Blocking studies with monoclonal antibodies revealed that the migration of neutrophils was mediated by the CR3 adhesion molecule (CD11b/CD18) on the neutrophils. IL-1beta-treated epithelial cells caused neutrophil movement via the secretion of chemoattractants. The most potent chemoattractant released by the epithelial cells was found to be IL-8, because the IL-1beta-induced migration was inhibited for 75 +/- 10% by the addition of an antibody against IL-8. After apical stimulation of the epithelial cells with an optimal concentration of IL-1beta, 27 +/- 4 ng/ml IL-8 was found in the supernatant at the apical side of epithelial cells. Platelet-activating factor (PAF) synthesis by the epithelial cells did not play a role in neutrophil transmigration, as was demonstrated by the lack of inhibition of this process after addition of the PAF-receptor antagonist WEB 2086. We conclude that the movement of neutrophils across airway epithelial cell monolayers occurs preferentially in the physiologic basolateral-to-apical direction, indicating that the polarity of epithelial cells is important for neutrophil transmigration.
为了研究中性粒细胞从血流进入肺气道的机制，我们研究了人中性粒细胞在人气道上皮细胞单层上的跨膜迁移，包括从顶侧到基底侧方向以及更符合生理情况的从基底侧到顶侧方向。人中性粒细胞在人气道上皮H292细胞系细胞和原代支气管上皮细胞单层上的迁移，在向静息上皮细胞添加趋化因子后以及通过白细胞介素-1β（IL-1β）刺激的上皮细胞时，最有效地发生在基底侧到顶侧方向。用单克隆抗体进行的阻断研究表明，中性粒细胞的迁移是由中性粒细胞上的CR3黏附分子（CD11b/CD18）介导的。IL-1β处理的上皮细胞通过分泌趋化因子引起中性粒细胞移动。发现上皮细胞释放的最有效的趋化因子是IL-8，因为添加抗IL-8抗体可使IL-1β诱导的迁移受到75±10%的抑制。在用最佳浓度的IL-1β对上皮细胞进行顶侧刺激后，在上皮细胞顶侧的上清液中发现了27±4 ng/ml的IL-8。上皮细胞合成血小板活化因子（PAF）在中性粒细胞跨膜迁移中不起作用，这一点通过添加PAF受体拮抗剂WEB 2086后该过程未受抑制得以证明。我们得出结论，中性粒细胞跨气道上皮细胞单层的移动优先发生在生理上的基底侧到顶侧方向，这表明上皮细胞的极性对中性粒细胞跨膜迁移很重要。
