Lampugnani M G, Caveda L, Breviario F, Del Maschio A, Dejana E
Istituto Mario Negri, Laboratory of Vascular Biology, Milano, Italy.
Baillieres Clin Haematol. 1993 Sep;6(3):539-58. doi: 10.1016/s0950-3536(05)80187-8.
Endothelial monolayer forms the main barrier to the passage of macromolecules and circulating cells from blood to tissues. This property is regulated by intercellular junctions. These are complex structures formed by transmembrane adhesive molecules linked to a network of cytoplasmic cytoskeletal proteins. Endothelial junctions vary in number and organization along the vascular tree. Some transmembrane components of endothelial junctions have recently been identified. One is specifically expressed by endothelial cells (cadherin-5) while others (such as PECAM-1 and integrins) are also present in other cell types. The mechanisms that regulate the opening and the closure of endothelial junctions are still obscure. It is possible that inflammatory agents increase permeability by binding to specific receptors on the endothelial membrane. This would lead to the generation of intracellular signals causing cytoskeletal reorganization and opening of interendothelial gaps. This general sequence of events, however, seems to follow specific routes for different stimuli. In fact, permeability-increasing agents differ in the type of intracellular second messenger they trigger, for the time course of their effect, and for their specificity for the endothelium of different vascular districts. Endothelial junctions also regulate leukocyte extravasation. Endothelial cells actively contribute to this process by expressing adhesive molecules on their surface and by releasing chemotactic cytokines. Once leukocytes have adhered to the endothelium, a coordinated opening of interendothelial junctions occurs. The mechanism by which this takes place is unknown but it might resemble that triggered by soluble inflammatory mediators.
内皮单层形成了大分子和循环细胞从血液进入组织的主要屏障。这一特性受细胞间连接调控。这些连接是由与细胞质细胞骨架蛋白网络相连的跨膜黏附分子形成的复杂结构。内皮连接在血管树中的数量和组织形式各不相同。内皮连接的一些跨膜成分最近已被确定。一种是内皮细胞特异性表达的（钙黏蛋白-5），而其他一些（如血小板内皮细胞黏附分子-1和整合素）也存在于其他细胞类型中。调节内皮连接开放和关闭的机制仍不清楚。炎症因子可能通过与内皮细胞膜上的特定受体结合来增加通透性。这将导致细胞内信号的产生，引起细胞骨架重组和内皮间隙的开放。然而，这一事件的一般顺序似乎因不同刺激而遵循特定途径。事实上，增加通透性的因子在它们触发的细胞内第二信使类型、作用的时间进程以及对不同血管区域内皮的特异性方面存在差异。内皮连接还调节白细胞渗出。内皮细胞通过在其表面表达黏附分子和释放趋化细胞因子积极参与这一过程。一旦白细胞黏附在内皮上，内皮间连接就会协同开放。这一过程发生的机制尚不清楚，但可能类似于由可溶性炎症介质触发的机制。
