Madara J L, Nash S, Moore R, Atisook K
Monogr Pathol. 1990(31):306-24.
The major and rate-limiting barrier to transepithelial permeation in the intestine is the intercellular tight junction. Tight junction structure is often cell type specific and general but imperfect correlates between tight junction structure and permeability exist. The structure and permeability of this key barrier is not static and can be regulated physiologically. The means of regulation appears to involve the cytoskeleton of neighboring epithelial cells (particularly absorptive cells). Meal-related solutes--nutrients such as glucose--can reversibly enhance the permeability of absorptive cell tight junctions. Although this may substantially enhance the ability of the small intestine to harvest meal-related nutrients, it is conceivable that this may also result in transient exposure of the subepithelial compartment to potentially noxious lumenal compounds. Some features found in many intestinal disease states such as PMN migration across the epithelium may also result in transient barrier defects. With PMN transmigration it is clear that even macromolecules may permeate junctions being impaled by PMNs. When disease processes finally result in focal epithelial denudation, the epithelium has the potential of resealing such defects with remarkable efficiency. The preceding discussion highlights how dynamic the tight junction is and sets the stage for future work aimed at understanding the initial signaling events and intracellular cascade(s) that allow this major barrier to demonstrate such plasticity.
肠道中跨上皮渗透的主要限速屏障是细胞间紧密连接。紧密连接结构通常具有细胞类型特异性，并且紧密连接结构与通透性之间存在一般但并不完美的相关性。这一关键屏障的结构和通透性并非一成不变，可受到生理调节。调节方式似乎涉及相邻上皮细胞（尤其是吸收细胞）的细胞骨架。与进食相关的溶质——如葡萄糖等营养物质——可可逆地增强吸收细胞紧密连接的通透性。尽管这可能会显著提高小肠获取与进食相关营养物质的能力，但可以想象，这也可能导致上皮下腔室短暂暴露于潜在有害的管腔化合物中。许多肠道疾病状态中出现的一些特征，如中性粒细胞跨上皮迁移，也可能导致短暂的屏障缺陷。在中性粒细胞迁移过程中，很明显甚至大分子也可能透过被中性粒细胞刺穿的连接。当疾病过程最终导致局灶性上皮剥脱时，上皮具有以显著效率重新封闭此类缺陷的潜力。上述讨论突出了紧密连接的动态性，并为未来旨在理解使这一主要屏障展现出如此可塑性的初始信号事件和细胞内级联反应的研究奠定了基础。
