摘要：

The single -thick intestinal epithelium forms a crucial barrier between the and environment, and is modeled in vitro by a monolayer of polarized, highly differentiated T84 epithelial impermeable to most macromolecules because of functional intercellular tight junctions. Absence of a permeability across the monolayer, either transcellular or paracellular, is indicated by development of a transepithelial electrical resistance of > or = 1000 ohm-cm2, reported to be markedly diminished by exposure to a T lymphocyte cytokine, . We sought to define this phenomenon in four ways by determining its duration and reversibility; the uniqueness of type II () as opposed to type I (alpha) ; the surface of the polarized columnar epithelium likely involved in responding to ; and whether a specific surface receptor on the epithelial participates in the response. Using a special apparatus that allows differential cytokine exposure of monolayer surfaces, our data demonstrate 1) only the monolayer's basolateral surface is responsive, whereas the apical (microvillous) surface is no; 2) the alteration in electrical resistance of epithelium is prolonged (5 days), even after a single (24 h) exposure to , but nevertheless is reversible; 3) the effect is likely receptor-ligand mediated, because it can be partially blocked by receptor-specific monoclonal Ig; 4) an alteration in tight junction function (a paracellular pathway) rather than necrosis or a transcellular pathway is responsible for -induced monolayer dysfunction because permeability to a 44,000() did not increase, and intracytoplasmic T84 enzymes were not released into the media; and 5) the biologic phenomenon could not be induced by a species (alpha) of class I , making reasonably unique in this regard. Given the proximity; activation status, and capacity of T lymphocytes for in mucosa, we suggest that -induced changes in epithelial permeability may be a major cause of altered intestinal barrier function in vivo.

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