Interplay between shear stress and adhesion on neutrophil locomotion
Interplay between shear stress and adhesion on neutrophil locomotion
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DOI：
10.1529/biophysj.105.079418
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发表时间：
2007-01-01
影响因子：
3.4
通讯作者：
Hammer, Daniel A.
中科院分区：
文献类型：
--
作者：
Smith, Lee A.;Aranda-Espinoza, Helim;Hammer, Daniel A.
在炎症反应中，白细胞在炎症内皮细胞管腔内的移动是在牢固的粘连之后的关键步骤。一旦牢固地附着，细胞就会扩散，要么通过单个血管内皮细胞进行渗出，要么迁移到紧密的连接处，然后渗出到损伤或感染的地方。关于中性粒细胞扩散或运动的机制，或运动如何受到物理环境的影响，人们知之甚少。本研究采用E-选择素、E-选择素/PECAM-1和E-选择素/ICAM-1重组蛋白的平行板流动室，系统地研究了黏附配体的类型和剪切力对中性粒细胞运动的影响。我们发现，黏附配体的水平和类型以及剪切率在影响迁移的几个指标方面是相互交织的，如迁移速度、随机迁移率、迁移指数和细胞沿流动方向移动的百分比。在含有高水平PECAM-1的表面上，当剪切速率为180时，与无流动时相比，随机运动性增加了近一倍。在含有ICAM-1的表面，中性粒细胞随机运动对剪切率的响应较弱，当剪切率从静止状态增加到180时略有下降，而在1000 S(-1)时仅略高于无血流时的水平。在静态和流动条件下，随着E-选择素和PECAM-1表面浓度的增加，随机迁移率增加。我们的发现表明，内皮细胞可能通过在炎症部位呈递各种黏附配体来调节中性粒细胞在毛细血管后小静脉中的迁移。
Leukocyte locomotion over the lumen of inflamed endothelial cells is a critical step, following firm adhesion, in the inflammatory response. Once firmly adherent, the cell will spread and will either undergo diapedesis through individual vascular endothelial cells or will migrate to tight junctions before extravasating to the site of injury or infection. Little is known about the mechanisms of neutrophil spreading or locomotion, or how motility is affected by the physical environment. We performed a systematic study to investigate the effect of the type of adhesive ligand and shear stress on neutrophil motility by employing a parallel-plate flow chamber with reconstituted protein surfaces of E-selectin, E-selectin/PECAM-1, and E-selectin/ICAM-1. We find that the level and type of adhesive ligand and the shear rate are intertwined in affecting several metrics of migration, such as the migration velocity, random motility, index of migration, and the percentage of cells moving in the direction of flow. On surfaces with high levels of PECAM-1, there is a near doubling in random motility at a shear rate of 180 s(-1) compared to the motility in the absence of flow. On surfaces with ICAM-1, neutrophil random motility exhibits a weaker response to shear rate, decreasing slightly when shear rate is increased from static conditions to 180 s(-1), and is only slightly higher at 1000 s(-1) than in the absence of flow. The random motility increases with increasing surface concentrations of E-selectin and PECAM-1 under static and flow conditions. Our findings illustrate that the endothelium may regulate neutrophil migration in postcapillary venules through the presentation of various adhesion ligands at sites of inflammation.