Smith Lee A, Aranda-Espinoza Helim, Haun Jered B, Hammer Daniel A
Department of Chemical and Biomolecular Engineering, and Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Biophys J. 2007 Jan 15;92(2):632-40. doi: 10.1529/biophysj.105.079418. Epub 2006 Oct 27.
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.
在炎症反应中，白细胞在内皮细胞管腔上的移动是继牢固黏附之后的关键步骤。一旦牢固黏附，细胞就会铺展，要么通过单个血管内皮细胞进行穿胞作用，要么迁移至紧密连接部位，然后外渗到损伤或感染部位。关于中性粒细胞铺展或移动的机制，以及运动性如何受到物理环境的影响，我们所知甚少。我们进行了一项系统性研究，通过使用具有重组E-选择素、E-选择素/血小板内皮细胞黏附分子-1（PECAM-1）和E-选择素/细胞间黏附分子-1（ICAM-1）蛋白表面的平行平板流动腔，来研究黏附配体类型和剪切应力对中性粒细胞运动性的影响。我们发现，黏附配体的水平和类型以及剪切速率在影响迁移的几个指标方面相互交织，如迁移速度、随机运动性、迁移指数以及沿血流方向移动的细胞百分比。在PECAM-1水平较高的表面，与无流动时相比，在剪切速率为180 s⁻¹时随机运动性几乎翻倍。在ICAM-1表面，中性粒细胞随机运动性对剪切速率的反应较弱，当剪切速率从静态条件增加到180 s⁻¹时略有下降，并且在1000 s⁻¹时仅比无流动时略高。在静态和流动条件下，随机运动性随E-选择素和PECAM-1表面浓度的增加而增加。我们的研究结果表明，内皮细胞可能通过在炎症部位呈现各种黏附配体来调节中性粒细胞在毛细血管后微静脉中的迁移。
