Mundhekar Ameya N, Bullard Daniel C, Kucik Dennis F
Department of Biomedical Engineering, University of Alabama at Birmingham, 35294, USA.
Am J Physiol Cell Physiol. 2006 Jul;291(1):C130-7. doi: 10.1152/ajpcell.00261.2005.
Endothelial cell junctions are thought to be preferential sites for transmigration. However, the factors that determine the site of transmigration are not well defined. Our data show that the preferential role of endothelial cell junctions is not limited to transmigration but extends to earlier steps of leukocyte recruitment, such as rolling and arrest. We used primary mouse neutrophils and mouse aortic endothelium in a flow chamber system to compare adhesive interactions near endothelial cell junctions to interactions over endothelial cell centers. We found differences in both rolling velocity and arrest frequency for neutrophils at endothelial cell junctions vs. more central areas of endothelial cells. Differences were governed by adhesion molecule interactions, not local topography. Interestingly, the role of particular adhesion molecules depended on their location on the endothelial cell surface. Although ICAM-1 stabilized and slowed rolling over central areas of the cell, it did not influence rolling velocity over endothelial cell junctions. P-selectin and VCAM-1 were more important for rolling near endothelial cell junctions than E-selectin. This demonstrates that adhesive properties of endothelial cell junctions influence early events in the adhesion cascade, which may help explain how leukocytes are localized to sites of eventual transmigration.
内皮细胞连接被认为是迁移的优先位点。然而，决定迁移位点的因素尚未明确界定。我们的数据表明，内皮细胞连接的优先作用不仅限于迁移，还延伸至白细胞募集的早期步骤，如滚动和黏附。我们在流动腔系统中使用原代小鼠中性粒细胞和小鼠主动脉内皮，比较内皮细胞连接处附近的黏附相互作用与内皮细胞中心区域的相互作用。我们发现，在内皮细胞连接处与内皮细胞更中央区域相比，中性粒细胞的滚动速度和黏附频率存在差异。差异由黏附分子相互作用决定，而非局部地形。有趣的是，特定黏附分子的作用取决于它们在内皮细胞表面的位置。尽管ICAM-1使细胞中央区域的滚动稳定并减缓，但它并不影响内皮细胞连接处的滚动速度。P-选择素和VCAM-1在内皮细胞连接处附近的滚动中比E-选择素更重要。这表明内皮细胞连接处的黏附特性影响黏附级联反应中的早期事件，这可能有助于解释白细胞如何定位于最终迁移的位点。
