title: Rapid lamina propria retraction and zipper-like constriction of the epithelium preserves the epithelial lining in human small intestine exposed to ischaemia-reperfusion.
abstract: To ensure a sufficient barrier between a host and noxious luminal content, the intestinal epithelium must be equipped with efficient mechanisms to limit damage to the epithelial lining. Using a human model, we were able to investigate these mechanisms in the human gut exposed to ischaemia-reperfusion (IR) over the time course of 150 min. In 10 patients a part of jejunum, to be removed for surgical reasons, was selectively exposed to IR. Control tissue was collected, as well as tissue exposed to 30 min of ischaemia with 0, 30 or 120 min of reperfusion. Haematoxylin/eosin staining demonstrated the appearance of subepithelial spaces following 30 min of ischaemia, while the epithelial lining remained intact at this stage. Western blot for myosin light chain kinase (MLCK) revealed a significant increase in protein levels after ischaemia (p < 0.01), and selective staining of MLCK and phosphorylated MLC (pMLC) in lamina propria muscle fibres indicated that appearance of subepithelial spaces was a consequence of active villus contraction. Early during reperfusion, accumulation of pMLC was observed exclusively at the basal side of enterocytes that had lost contact with the collagen-IV-positive basement membrane. These epithelial sheets were pulled together like a zipper, even before these cells were shed. This constriction, verified by increased F-actin and pMLC double staining, accounted for a 45% reduction in virtual wound surface (p < 0.001) at 30 min of reperfusion. In addition, these mechanisms were involved in resealing remaining small epithelial defects, resulting in a fully restored epithelial lining within 120 min of reperfusion. In conclusion, we show in a human in vivo model that the human jejunum has the ability to preserve the epithelial lining during intestinal IR by rapid lamina propria contraction and zipper-like constriction of epithelial cells that are to be shed into the lumen. These newly described phenomena limit exposure to noxious luminal content.
authors.affiliation: Department of Surgery, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Joep
authors.initials: J
authors.lastname: Grootjans
authors.forename: Geertje
authors.initials: G
authors.lastname: Thuijls
authors.forename: Joep P M
authors.initials: JP
authors.lastname: Derikx
authors.forename: Ronald M
authors.initials: RM
authors.lastname: van Dam
authors.forename: Cornelis H C
authors.initials: CH
authors.lastname: Dejong
authors.forename: Wim A
authors.initials: WA
authors.lastname: Buurman
mesh_terms: D000199:Actins / Q000378:metabolism / Q000502:physiology; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007421:Intestine, Small / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009119:Muscle Contraction / Q000502:physiology; D009130:Muscle, Smooth / Q000503:physiopathology; D018994:Myosin Light Chains / Q000378:metabolism / Q000502:physiology; D009219:Myosin-Light-Chain Kinase / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D014945:Wound Healing / Q000502:physiology
chemical_list: D000199:Actins; D018994:Myosin Light Chains; D009219:Myosin-Light-Chain Kinase