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dc.contributor.authorKiesslich, Ralf
dc.contributor.authorGoetz, Martin
dc.contributor.authorAngus, Elizabeth M
dc.contributor.authorHu, Qiuping
dc.contributor.authorGuan, Yanfang
dc.contributor.authorPotten, Christopher S
dc.contributor.authorAllen, Terence D
dc.contributor.authorNeurath, Markus F
dc.contributor.authorShroyer, Noah F
dc.contributor.authorMontrose, Marshall H
dc.contributor.authorWatson, Alastair
dc.date.accessioned2009-06-30T10:40:46Z
dc.date.available2009-06-30T10:40:46Z
dc.date.issued2007-12
dc.identifier.citationIdentification of epithelial gaps in human small and large intestine by confocal endomicroscopy. 2007, 133 (6):1769-78 Gastroenterologyen
dc.identifier.issn1528-0012
dc.identifier.pmid18054549
dc.identifier.doi10.1053/j.gastro.2007.09.011
dc.identifier.urihttp://hdl.handle.net/10541/71914
dc.description.abstractBACKGROUND & AIMS: Confocal endomicroscopy is an emerging technology that poses the endoscopist with challenges for identifying epithelial structures in the human intestine. We have shown previously that the murine intestinal epithelium is punctuated by gaps caused by cell shedding. The goals of this study were to determine if confocal endomicroscopy could resolve the presence of human epithelial gaps and whether a proinflammatory cytokine could increase cell shedding. METHODS: Intestinal mucosa was imaged after staining with acriflavine. Confocal endomicroscopy of 17 patients yielded 6277 images from the human terminal ileum and rectum. Results were validated by parallel studies of anesthetized mice (wild-type and Math1(DeltaIntestine)) using rigid confocal probe microscopy, 2-photon/confocal microscopy, and scanning electron microscopy. RESULTS: Human terminal ileal and rectal epithelium revealed unstained areas with the diameter of an individual epithelial cell, with 2 distinct morphologies. One had a "target" appearance, shown by mouse studies to be goblet cells. The other morphology had no nucleus and was observed by rigid confocal probe microscopy and scanning electron microscopy in the villi of Math1(DeltaIntestine) mice, which lack goblet cells. In the mouse, tumor necrosis factor alpha (0.33 microg/g intraperitoneally) increases cell shedding by 27-fold and caused loss of barrier function across 20% of resultant gaps. CONCLUSIONS: Confocal endomicroscopy can distinguish between epithelial discontinuities (gaps) and goblet cells in human intestine. Results suggest that the sealing of epithelial gaps must be considered as a component of the intestinal barrier and has potential implications for intestinal barrier dysfunction in human disease.
dc.language.isoenen
dc.subjectTumour Necrosisen
dc.subject.meshAdolescent
dc.subject.meshAdult
dc.subject.meshAged
dc.subject.meshAnimals
dc.subject.meshColonoscopy
dc.subject.meshEpithelial Cells
dc.subject.meshFemale
dc.subject.meshHumans
dc.subject.meshIntestine, Large
dc.subject.meshIntestine, Small
dc.subject.meshMale
dc.subject.meshMice
dc.subject.meshMicroscopy, Confocal
dc.subject.meshMiddle Aged
dc.subject.meshTumor Necrosis Factor-alpha
dc.titleIdentification of epithelial gaps in human small and large intestine by confocal endomicroscopy.en
dc.typeArticleen
dc.contributor.departmentI Medical Clinic, University of Mainz, Mainz, Germany.en
dc.identifier.journalGastroenterologyen
html.description.abstractBACKGROUND & AIMS: Confocal endomicroscopy is an emerging technology that poses the endoscopist with challenges for identifying epithelial structures in the human intestine. We have shown previously that the murine intestinal epithelium is punctuated by gaps caused by cell shedding. The goals of this study were to determine if confocal endomicroscopy could resolve the presence of human epithelial gaps and whether a proinflammatory cytokine could increase cell shedding. METHODS: Intestinal mucosa was imaged after staining with acriflavine. Confocal endomicroscopy of 17 patients yielded 6277 images from the human terminal ileum and rectum. Results were validated by parallel studies of anesthetized mice (wild-type and Math1(DeltaIntestine)) using rigid confocal probe microscopy, 2-photon/confocal microscopy, and scanning electron microscopy. RESULTS: Human terminal ileal and rectal epithelium revealed unstained areas with the diameter of an individual epithelial cell, with 2 distinct morphologies. One had a "target" appearance, shown by mouse studies to be goblet cells. The other morphology had no nucleus and was observed by rigid confocal probe microscopy and scanning electron microscopy in the villi of Math1(DeltaIntestine) mice, which lack goblet cells. In the mouse, tumor necrosis factor alpha (0.33 microg/g intraperitoneally) increases cell shedding by 27-fold and caused loss of barrier function across 20% of resultant gaps. CONCLUSIONS: Confocal endomicroscopy can distinguish between epithelial discontinuities (gaps) and goblet cells in human intestine. Results suggest that the sealing of epithelial gaps must be considered as a component of the intestinal barrier and has potential implications for intestinal barrier dysfunction in human disease.


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