Chemoattractant signals and β2 integrin occupancy at apical endothelial contacts combine with shear stress signals to promote transendothelial neutrophil migration
Chemoattractant signals and β2 integrin occupancy at apical endothelial contacts combine with shear stress signals to promote transendothelial neutrophil migration
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DOI：
10.4049/jimmunol.173.12.7282
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发表时间：
2004-12-15
影响因子：
4.4
通讯作者：
Alon, R
中科院分区：
文献类型：
--
作者：
Cinamon, G;Shinder, V;Alon, R
淋巴细胞跨内皮迁移（TEM）是由流体剪切信号和根尖内皮趋化因子促进的。通过研究这些信号在中性粒细胞在不同活化HUVEC中的迁移中的作用，我们对中性粒细胞如何整合多种内皮信号来促进TEM有了新的见解。中性粒细胞以β 2整合素依赖的方式与高度激活的HUVEC交叉，但独立于剪切。相比之下，中性粒细胞在静止或适度激活的内皮中迁移，在低水平β(2)整合素配体活性的情况下，内皮呈现的化学引诱剂显著增强了中性粒细胞在生理剪切应力和完整β(2)整合素的应用条件下的迁移。在TEM之前和过程中，剪切应力信号均刺激中性粒细胞广泛内陷到根尖内皮界面。一组内陷中性粒细胞在1分钟内通过单个内皮细胞完成跨细胞浸润。我们的研究结果表明，粘附的中性粒细胞低水平占用β(2)整合素，只有在适当地耦合刺激剪切应力和在根尖中性粒细胞-内皮细胞界面转导的化学引诱信号时，才能介导TEM。
Lymphocyte transendothelial migration (TEM) is promoted by fluid shear signals and apical endothelial chemokines. Studying the role of these signals in neutrophil migration across differently activated HUVEC in a flow chamber apparatus, we gained new insights into how neutrophils integrate multiple endothelial signals to promote TEM. Neutrophils crossed highly activated HUVEC in a beta2 integrin-dependent manner but independently of shear. In contrast, neutrophil migration across resting or moderately activated endothelium with low-level beta(2) integrin ligand activity was dramatically augmented by endothelial-presented chemoattractants, conditional to application of physiological shear stresses and intact beta2 integrins. Shear stress signals were found to stimulate extensive neutrophil invaginations into the apical endothelial interface both before and during TEM. A subset of invaginating neutrophils completed transcellular diapedesis through individual endothelial cells within < 1 min. Our results suggest that low-level occupancy of beta(2) integrins by adherent neutrophils can mediate TEM only if properly coupled to stimulatory shear stress and chemoattractant signals transduced at the apical neutrophil-endothelial interface.