摘要：

Gut 2004;53:494-500. doi: 10.1136/gut.2003.028506 Background: Chronic stress affects the course of inflammatory bowel disease and experimental colitis, and may also initiate intestinal inflammation in rats. Aim: To investigate the effects of stress on the M cell containing follicle associated epithelium, specialised in antigen uptake. Subjects and methods: Wistar rats were submitted to acute water avoidance stress for one hour or chronic water avoidance stress for 1 hour/day for 10 consecutive days. Permeability to [.sup.51]Cr-EDTA, horseradish peroxidase, and chemically killed Escherichia coli K-12 was studied in both villus and follicle associated epithelium in Ussing chambers. Segments were further examined by light, electron, and confocal microscopy. Results: Acute stress increased horseradish peroxidase flux in villus as well as in follicle associated epithelium. Chronic stress further increased permeability to horseradish peroxidase in villus and follicle associated epithelium, in the latter by almost fourfold. Moreover, chronic stress induced over 30 times increased E coli passage in follicle associated epithelium whereas there was no significant increase in villus epithelium. Bacterial uptake was confirmed by confocal microscopy showing fluorescent bacteria penetrating and passing through the epithelial surface. Conclusions: These results show that the barrier function of follicle associated epithelium can be modulated, and that chronic stress enhances the uptake of luminal antigens and bacteria via the follicle associated epithelium. This can increase antigen exposure in Peyer's patches thereby having implications in the initiation of proinflammatory immune responses within the intestinal mucosa. ********** The follicle associated epithelium (FAE) that covers Peyer's patches is an important route for the uptake of antigens and bacteria into the intestinal mucosa. (1 2) The FAE contains membranous (M) cells and thereby it has unique biochemical properties, facilitating adherence, uptake, and immunological sampling of microorganisms. (2) Adherent materials are endocytosed by M cells and transported to the underlying lymphoid tissue. It is well accepted that inflammatory bowel disease (IBD) is associated with an antigenic load from luminal dietary products and bacteria. (3) As FAE is an entry site for bacteria, and IBD is associated with an increased immune reaction to non-specific bacteria, (4 5) dysfunction in the regulation of FAE could be involved in IBD. The possibility of dysregulated FAE in IBD is strengthened by the fact that the earliest observable signs of Crohn's disease (CD) are aphthoid ulcers originating from the FAE. (6 7) It is believed that chronic stress modulates inflammatory activity in IBD. (8 9) Severe stress episodes are an important risk factor for the development and reactivation of intestinal inflammation in rodents (10) and in humans, (11 12) Moreover, environmental stress can alter the course of CD. (13) In animal models, stress induced mucosal dysfunction mainly involves corticotropin releasing hormone, mast cells, and cholinergic neurones. (14-16) In rat villus epithelium (VE), acute stress increases intestinal permeability to macromolecules without causing changes in gut morphology. (17-19) However, when exposing rats to repetitive stress, the outcome is a further increase in permeability, bacterial attachment, mast cell hyperplasia, and initiation of inflammation. (20 21) Although FAE is an important route of...

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