Abstract:Ileocolonoscopy and biopsies of patients with spondylarthropathy reveal gut inflammation in 62% of cases. In order to better understand the pathogenetic mechanisms of spondylarthropathy-related gut inflammation, the follicle-associated epithelium was examined. Biopsies from nine controls and 18 patients with spondylarthropathy were studied by electronmicroscopy. Membranous (M) cells were investigated in normal and inflamed ileum. In normal mucosa, M-cells were scarce whereas in inflamed mucosa their number was… Show more
“…2,37 M cells constitute approximately 10% of the FAE, however, this number can be increased during intestinal inflammation. 38,39 M cells lack a developed microvillus border and glycocalyx coat, which facilitates access for luminal pathogens and thereby the uptake increases. 2,37 There are large differences between different species regarding markers for M cells.…”
The follicle-associated epithelium (FAE), covering Peyer's patches, provides a route of entry for antigens and microorganisms. Animal studies showed enhanced antigen and bacterial uptake in FAE, but no study on barrier function of human FAE has been reported. Our aim was to characterize the normal barrier properties of human FAE. Specimens of normal ileum were taken from 30 patients with noninflammatory colonic disease. Villus epithelium (VE) and FAE were identified and mounted in Ussing chambers. Permeability to 51 Cr-EDTA, transmucosal flux of the protein antigen, horseradish peroxidase (HRP), and transport of fluorescent Escherichia coli (chemically killed K-12 and live HB101) were measured. Uptake mechanisms were studied by confocal-and transmission electron microscopy, and by using pharmacological inhibitors in an in vitro coculture model of FAE and in human ileal FAE. HRP flux was substantially higher in FAE than in VE, and was reduced by an amiloride analog. Electron microscopy showed HRP-containing endosomes. Transport of E. coli K-12 and HB101 was also augmented in FAE and was confirmed by confocal microscopy. In vitro coculture experiments and electron microscopy revealed actin-dependent, mainly transcellular, uptake of E. coli K-12 into FAE. 51 Cr-EDTA permeability was equal in FAE and VE. Augmented HRP flux and bacterial uptake but similar paracellular permeability, suggest functional variations of transcellular transport in the FAE. We show for the first time that FAE of human ileum is functionally distinct from regular VE, rendering the FAE more prone to bacterial-epithelial cell interactions and delivery of antigens to the mucosal immune system.
“…2,37 M cells constitute approximately 10% of the FAE, however, this number can be increased during intestinal inflammation. 38,39 M cells lack a developed microvillus border and glycocalyx coat, which facilitates access for luminal pathogens and thereby the uptake increases. 2,37 There are large differences between different species regarding markers for M cells.…”
The follicle-associated epithelium (FAE), covering Peyer's patches, provides a route of entry for antigens and microorganisms. Animal studies showed enhanced antigen and bacterial uptake in FAE, but no study on barrier function of human FAE has been reported. Our aim was to characterize the normal barrier properties of human FAE. Specimens of normal ileum were taken from 30 patients with noninflammatory colonic disease. Villus epithelium (VE) and FAE were identified and mounted in Ussing chambers. Permeability to 51 Cr-EDTA, transmucosal flux of the protein antigen, horseradish peroxidase (HRP), and transport of fluorescent Escherichia coli (chemically killed K-12 and live HB101) were measured. Uptake mechanisms were studied by confocal-and transmission electron microscopy, and by using pharmacological inhibitors in an in vitro coculture model of FAE and in human ileal FAE. HRP flux was substantially higher in FAE than in VE, and was reduced by an amiloride analog. Electron microscopy showed HRP-containing endosomes. Transport of E. coli K-12 and HB101 was also augmented in FAE and was confirmed by confocal microscopy. In vitro coculture experiments and electron microscopy revealed actin-dependent, mainly transcellular, uptake of E. coli K-12 into FAE. 51 Cr-EDTA permeability was equal in FAE and VE. Augmented HRP flux and bacterial uptake but similar paracellular permeability, suggest functional variations of transcellular transport in the FAE. We show for the first time that FAE of human ileum is functionally distinct from regular VE, rendering the FAE more prone to bacterial-epithelial cell interactions and delivery of antigens to the mucosal immune system.
“…The surface of the dome region is covered by the follicle-associated epithelium (FAE) comprising M (microfold) cells (13), whose function is to selectively sample and transport luminal Ags, including proteins and microorganisms (14). The numbers of M cells vary between species, ranging from percentages as low as 2% of the FAE in humans (15) to an almost homogeneous population in the ruminant ileal Peyer's patch (16,17). The differentiation and uptake processes of M cells are poorly defined (18), mainly because their scarcity in the intestinal mucosa has hampered their cellular and biochemical studies.…”
Section: Peyer's Patches M Cells and Dendritic Cells (Dc) 3 In Intementioning
An important activity of mucosal surfaces is the production of Ab referred to as secretory IgA (SIgA). SIgA serves as the first line of defense against microorganisms through a mechanism called immune exclusion. In addition, SIgA adheres selectively to M cells in intestinal Peyer’s patches, thus mediating the transepithelial transport of the Ab molecule from the intestinal lumen to underlying gut-associated organized lymphoid tissue. In Peyer’s patches, SIgA binds and is internalized by dendritic cells in the subepithelial dome region. When used as carrier for Ags in oral immunization, SIgA induces mucosal and systemic responses associated with production of anti-inflammatory cytokines and limits activation of dendritic cells. In terms of humoral immunity at mucosal surfaces, SIgA appears thus to combine properties of a neutralizing agent (immune exclusion) and of a mucosal immunopotentiator inducing effector immune responses in a noninflammatory context favorable to preserve local homeostasis of the gastrointestinal tract.
“…In conclusion, CCR6 seems to determine physiological and pathological immune responses generated within PPs particularly by influencing M-cell formation and DC-dependent T-cell stimulation. Because these structures are potential sites for initial abnormalities found in Crohn's disease, 38,39 the influence of CCR6 expression with inflammatory bowel disease pathology needs to be further investigated.…”
Section: Y Enterocolitica Infection Of Ccr6mentioning
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