Masedunskas Andrius, King Judy A, Tan Fang, Cochran Ruth, Stevens Troy, Sviridov Dmitri, Ofori-Acquah Solomon F
Department of Cell Biology and Neuroscience, MSB 2348, University of South Alabama, Mobile, 36688-0002, USA.
FEBS Lett. 2006 May 15;580(11):2637-45. doi: 10.1016/j.febslet.2006.04.013. Epub 2006 Apr 21.
Transendothelial leukocyte migration is a major aspect of the innate immune response. It is essential in repair and regeneration of damaged tissues and is regulated by multiple cell adhesion molecules (CAMs) including members of the immunoglobulin (Ig) superfamily. Activated leukocyte cell adhesion molecule (ALCAM/CD166) is an Ig CAM expressed by activated monocytes and endothelial cells. Hitherto, the functional relevance of ALCAM expression by endothelial cells and activated monocytes remained unknown. In this report, we demonstrate soluble recombinant human ALCAM significantly inhibited the rate of transendothelial migration of monocyte cell lines. Direct involvement of ALCAM in transendothelial migration was evident from the robust inhibition of this process by ALCAM blocking antibodies. However, soluble recombinant ALCAM had no impact on monocyte migration or adhesion to endothelium. Localization of ALCAM specifically at cell-cell junctions in endothelial cells supported its role in transendothelial migration. This study is the first to localize ALCAM to endothelial cell junctions and demonstrate a functional relevance for co-expression of ALCAM by activated monocytes and endothelial cells.
跨内皮白细胞迁移是先天性免疫反应的一个主要方面。它在受损组织的修复和再生中至关重要，并受多种细胞粘附分子（CAMs）调控，包括免疫球蛋白（Ig）超家族成员。活化白细胞细胞粘附分子（ALCAM/CD166）是一种由活化单核细胞和内皮细胞表达的Ig CAM。迄今为止，内皮细胞和活化单核细胞表达ALCAM的功能相关性尚不清楚。在本报告中，我们证明可溶性重组人ALCAM显著抑制单核细胞系的跨内皮迁移率。ALCAM阻断抗体对这一过程的强烈抑制表明ALCAM直接参与跨内皮迁移。然而，可溶性重组ALCAM对单核细胞迁移或与内皮的粘附没有影响。ALCAM特异性定位于内皮细胞的细胞间连接处，这支持了其在跨内皮迁移中的作用。本研究首次将ALCAM定位于内皮细胞连接处，并证明活化单核细胞和内皮细胞共表达ALCAM具有功能相关性。
