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- W2025171024 abstract "The lumen of the distal small intestine and colon represents an enormous reservoir of microbes and potentially toxic microbial products. Therefore, in addition to the absorption of water and nutrients, an important function of the gut is to serve as an effective barrier, limiting systemic contamination by intraluminal microbes or their products. Two approaches are commonly used in both clinical and experimental studies to assess the integrity of gut barrier function. One method estimates the degree of transmucosal movement of bacteria or yeast from the intestinal lumen to mesenteric lymph nodes (MLNs), other organs, or blood, a process referred to as microbial translocation. The other method quantitates the permeability of the gut to various water-soluble probes. Translocation usually is quantitated by enumerating viable colony-forming units in MLNs, liver, spleen, lung, and blood. Simply culturing MLNs or other organs, however, substantially underestimates the extent of translocation because most microbes breaching the epithelial barrier are killed.53 Thus, the apparent increases in translocation, which have been observed under a variety of pathologic circumstances, probably reflect the combined effects of increased transmucosal penetration by microbes and decreased killing of penetrating organisms by the host's antimicrobial defense mechanisms. To move from the lumen to the lamina propria, translocating microbes must breach the barrier imposed by the continuous epithelial lining of the intestine. Many species and strains of bacteria, such as Escherichia coli and Salmonella typhimurium, appear to translocate by moving through enterocytes, rather than by disrupting the junctional complexes between adjacent cells to traverse the epithelium via a paracellular route.3, 153 It is possible, however, that certain strains or species of bacteria pass through intercellular spaces.173 Moreover, if the epithelium is denuded or ulcerated, microbes can easily gain access to the lamina propria. After passing through the epithelial layer, bacteria can be ingested by macrophages and, if not killed, transported to regional lymph nodes. Microbes in the lamina propria also can directly enter lymphatics or capillaries. Theoretically, there are two possible routes for passive permeation of the epithelium by hydrophilic molecules and ions. One is the transcellular pathway, and the other is the paracellular pathway. Because current in biologic systems is carried by the movement of small ions (e.g., Na+ and Cl−), one way to assess permeability is by measuring electrical resistance. It is noteworthy therefore that the electrical resistance of the cytosolic membranes of both the apical and the basolateral surfaces of enterocytes is about 106 to 109 ohm⋅cm2,61, 117 whereas the normal transepithelial resistance for the small intestinal epithelium is much lower (102 ohm⋅cm2).47, 87 Accordingly, it seems most likely that permeation of hydrophilic solutes occurs mainly via the paracellular pathway. More than 85% of the passive permeation by ions is thought to be paracellular.52 The paracellular pathway consists of a water-filled channel formed by adjacent enterocytes. The tight junction between adjoining cells acts as a limiting barrier, controlling permeation via the paracellular pathway and enabling the normal intestinal epithelium to exhibit a phenomenon called selective permeability.66 As a consequence, the gut readily absorbs small molecules and ions (e.g., water, Na+, Cl−, amino acids). The transepithelial passage of potentially toxic or proinflammatory hydrophilic molecules with a Stokes radius greater than about 11.5 Å, however, is precluded.87 The tight junction (or zonula occludens) is a narrow band, which consists of several strands wrapping around the circumference of the apical portion of epithelial cells. The number of the strands correlates with the tightness of the junction.31, 32 In the intestine, the tight junctions of the villus epithelium have a higher number of strands and are more restrictive than the tight junctions in the epithelium of the crypts, which have a lower number of strands. Several specialized proteins, including ZO-1 and ZO-2, have been identified as components of the tight junction and are thought to play an important functional role in the regulation of paracellular permeability.6 The tight junction also is closely linked to the cytoskeleton by a circumferential ring of actin and myosin, located just below the zonula occludens.86, 88 Mucosal permeability to hydrophilic solutes is regulated under physiologic conditions by intracellular signals, which are transmitted to the tight junction and translated into constriction or dilation of the apical pore by dynamic changes in the cytoskeleton. Under pathologic conditions, derangements in the regulation of epithelial permeability also are associated with changes in the actin-based cytoskeleton." @default.
- W2025171024 created "2016-06-24" @default.
- W2025171024 creator A5016382132 @default.
- W2025171024 creator A5052569785 @default.
- W2025171024 date "1998-06-01" @default.
- W2025171024 modified "2023-09-26" @default.
- W2025171024 title "INTESTINAL EPITHELIAL HYPERPERMEABILITY" @default.
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