Babinska Anna, Kedees Mamdouh H, Athar Humra, Ahmed Tahir, Batuman Olcay, Ehrlich Yigal H, Hussain M Mahmood, Kornecki Elizabeth
Department of Anatomy/Cell Biology, State University of New York, Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, NY 11203, USA.
Thromb Haemost. 2002 Nov;88(5):843-50.
The F11 receptor (F11R) is a cell adhesion molecule (CAM), member of the immunoglobulin superfamily found on the surface of human platelets, and determined to play a role in platelet aggregation, secretion, adhesion and spreading. The same molecule is present also at tight junctions of endothelial cells (EC) where it is known as JAM and acts as a CAM through homophilic interactions. The role of F11R/JAM in the interaction of platelets with endothelial cells was investigated in the current studies. We report here that washed human platelets adhere specifically to a matrix made of immobilized, recombinant sF11R. Furthermore, platelets adhere to cytokine- (TNF-alpha, INF-gamma) stimulated human umbilical vein endothelial cells (HUVEC), and approximately 40-60% of the adhesive force is exerted by homophilic interactions between the F11R of platelets and EC. This is evidenced by the inhibition of platelet adhesion to endothelial cells by recombinant soluble form of the F11R, and by two F11R peptides with amino acid sequences of the N-terminal region, and in the 1(st) Ig fold of the F11R, respectively. This study suggests a role for F11R in the adhesion of platelets to cytokine-inflamed endothelial cells and thus in thrombosis and atherosclerosis induced in non-denuded blood vessels by inflammatory processes. Agents that block the F11R-mediated adhesion of platelets to EC may be of therapeutic value in controlling thrombosis and preventing heart attacks and stroke.
F11受体（F11R）是一种细胞粘附分子（CAM），属于免疫球蛋白超家族成员，存在于人类血小板表面，在血小板聚集、分泌、粘附和铺展过程中发挥作用。同一分子也存在于内皮细胞（EC）的紧密连接处，在那里它被称为连接粘附分子（JAM），并通过同源相互作用作为一种细胞粘附分子发挥作用。在当前研究中，对F11R/JAM在血小板与内皮细胞相互作用中的作用进行了研究。我们在此报告，洗涤后的人类血小板可特异性粘附于由固定化重组sF11R构成的基质。此外，血小板可粘附于细胞因子（肿瘤坏死因子-α、干扰素-γ）刺激的人脐静脉内皮细胞（HUVEC），且约40%-60%的粘附力是由血小板和内皮细胞的F11R之间的同源相互作用产生的。这一点通过F11R重组可溶性形式以及分别具有F11R N端区域氨基酸序列和F11R第1个免疫球蛋白折叠区域氨基酸序列的两种F11R肽对血小板与内皮细胞粘附的抑制作用得到证明。本研究表明F11R在血小板与细胞因子炎症内皮细胞的粘附中发挥作用，进而在炎症过程诱导的非剥脱性血管血栓形成和动脉粥样硬化中发挥作用。阻断F11R介导的血小板与内皮细胞粘附的药物在控制血栓形成以及预防心脏病发作和中风方面可能具有治疗价值。
