INTERFERON-GAMMA INDUCES A CELL-SURFACE PHENOTYPE SWITCH ON T84 INTESTINAL EPITHELIAL-CELLS
INTERFERON-GAMMA INDUCES A CELL-SURFACE PHENOTYPE SWITCH ON T84 INTESTINAL EPITHELIAL-CELLS
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DOI：
10.1152/ajpcell.1994.267.2.c402
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发表时间：
1994-08-01
影响因子：
--
通讯作者：
MADARA, JL
中科院分区：
文献类型：
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作者：
COLGAN, SP;PARKOS, CA;MADARA, JL
Intestinal epithelia are in intimate contact with submucosal and intraepithelial lymphocytes. The concentration of intraepithelial lymphocytes increases during inflammatory processes, and, when stimulated, these cells generate cytokines such as interferon-gamma (IFN-gamma). In this study, we examined the effect of recombinant human IFN-gamma on ion transport events in T84 cells, a crypt epithelial cell line widely used to study electrogenic Cl- secretion, the transport event responsible for mucosal hydration. Epithelial exposure to IFN-gamma brought about a marked attenuation in stimulated Cl- secretion, as measured by generation of short-circuit current (I-sc) This IFN-gamma-elicited decrease in the Cl- secretory response was present for a variety of specific agonists, appeared largely due to IFN-gamma interactions with the basolateral surface, and did not result from a defect in second messenger generation. Efflux and uptake studies were utilized to functionally define the individual cell surface transport proteins that participate in Cl- secretion and revealed that, in response to epithelial exposure to IFN-gamma, apical Cl- channels and basolateral Na+-K+-2Cl(-) cotransporters, K+ channels, and Na-K-adenosinetriphosphatase were all functionally downregulated. [H-3]bumetanide binding assays suggested that surface expression of the cotransporter was diminished by >70% after IFN-gamma preexposure. Concurrently, surface immunofluorescence studies revealed that epithelial exposure to IFN-gamma brought about the induction of major histocompatibility complex (MHC) class II molecule expression on T84 epithelial monolayers and markedly increased MHC class I surface expression. Finally, neutrophilepithelial adhesion studies revealed that preexposure of epithelial monolayers to IFN-gamma elicited a beta(2)-integrin-dependent induction of neutrophil adhesion. These results suggest a global ''phenotypic switch'' on the intestinal epithelial cell surface from one exhibiting classical epithelial transport function to one expressing significant immune accessory function.
