Martìn-Padura I, Lostaglio S, Schneemann M, Williams L, Romano M, Fruscella P, Panzeri C, Stoppacciaro A, Ruco L, Villa A, Simmons D, Dejana E
Istituto di Ricerche Farmacologiche Mario Negri, 20157 Milano, Italy.
J Cell Biol. 1998 Jul 13;142(1):117-27. doi: 10.1083/jcb.142.1.117.
Tight junctions are the most apical components of endothelial and epithelial intercellular cleft. In the endothelium these structures play an important role in the control of paracellular permeability to circulating cells and solutes. The only known integral membrane protein localized at sites of membrane-membrane interaction of tight junctions is occludin, which is linked inside the cells to a complex network of cytoskeletal and signaling proteins. We report here the identification of a novel protein (junctional adhesion molecule [JAM]) that is selectively concentrated at intercellular junctions of endothelial and epithelial cells of different origins. Confocal and immunoelectron microscopy shows that JAM codistributes with tight junction components at the apical region of the intercellular cleft. A cDNA clone encoding JAM defines a novel immunoglobulin gene superfamily member that consists of two V-type Ig domains. An mAb directed to JAM (BV11) was found to inhibit spontaneous and chemokine-induced monocyte transmigration through an endothelial cell monolayer in vitro. Systemic treatment of mice with BV11 mAb blocked monocyte infiltration upon chemokine administration in subcutaneous air pouches. Thus, JAM is a new component of endothelial and epithelial junctions that play a role in regulating monocyte transmigration.
紧密连接是内皮细胞和上皮细胞细胞间缝隙最顶端的组成部分。在内皮细胞中，这些结构在控制细胞旁对循环细胞和溶质的通透性方面发挥着重要作用。唯一已知定位于紧密连接膜 - 膜相互作用位点的整合膜蛋白是闭合蛋白，它在细胞内与细胞骨架和信号蛋白的复杂网络相连。我们在此报告鉴定出一种新型蛋白（连接粘附分子[JAM]），它选择性地集中在不同来源的内皮细胞和上皮细胞的细胞间连接处。共聚焦显微镜和免疫电子显微镜显示，JAM与紧密连接成分在细胞间缝隙的顶端区域共分布。编码JAM的cDNA克隆定义了一个由两个V型免疫球蛋白结构域组成的新型免疫球蛋白基因超家族成员。发现一种针对JAM的单克隆抗体（BV11）在体外可抑制单核细胞通过内皮细胞单层的自发迁移和趋化因子诱导的迁移。用BV11单克隆抗体对小鼠进行全身治疗可阻断趋化因子注入皮下气囊后单核细胞的浸润。因此，JAM是内皮细胞和上皮细胞连接的一个新成分，在调节单核细胞迁移中发挥作用。
