title: Induction of apoptosis before shedding of human intestinal epithelial cells.
abstract: OBJECTIVE
  Human intestinal epithelial cells (IECs) derive from stem cells at the crypt base and migrate along the so-called crypt-villus axis toward the intestinal lumen. As they reach the luminal surface in the colon or the villus tip in the small intestine, IECs are shed and their life cycle is terminated. The role of apoptosis during IEC migration along the crypt-villus axis has been subject to studies with conflicting results. In this study we use a novel approach to identify the initiation of apoptosis within normal human IECs.
  
  
  METHODS
  Normal mucosa from the large and small human intestine was analyzed employing a novel antibody directed against activated caspase-3--an early marker of apoptosis.
  
  
  RESULTS
  IECs initiate the apoptotic cascade as they approach the area of shedding before displaying evident morphological features of apoptosis. IECs of the small bowel also show caspase-3 activation in the small intestinal crypt base, whereas IECs of the colononic crypt base rarely show evidence of ongoing apoptosis.
  
  
  CONCLUSIONS
  These findings indicate that apoptosis is initiated in human IECs as they reach the luminal surface/villus tip and before shedding. Furthermore, they show that different sections of the intestinal tract vary significantly in the rate of IEC apoptosis, possibly reflecting their difference in susceptibility to epithelial cell neoplasia.
authors.affiliation: Institute of Internal Medicine I, University of Regensburg, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Grossmann
authors.forename: Kathrin
authors.initials: K
authors.lastname: Walther
authors.forename: Monika
authors.initials: M
authors.lastname: Artinger
authors.forename: Petra
authors.initials: P
authors.lastname: Rümmele
authors.forename: Matthias
authors.initials: M
authors.lastname: Woenckhaus
authors.forename: Jürgen
authors.initials: J
authors.lastname: Schölmerich
mesh_terms: D017209:Apoptosis; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D003106:Colon / Q000166:cytology / Q000201:enzymology; D004789:Enzyme Activation; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000166:cytology / Q000502:physiology*; D007421:Intestine, Small / Q000502:physiology
chemical_list: C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases