title: In vitro model of intestinal crypt abscess. A novel neutrophil-derived secretagogue activity.
abstract: In order to model crypt abscesses, a histological finding which correlates with disease activity in intestinal inflammation, human polymorphonuclear leukocytes (PMN) were layered onto monolayers of the human intestinal epithelial cell line T84, a crypt-like epithelium which is capable of Cl- secretion. Such PMN-epithelial interaction had no substantial effect on monolayer integrity or function. However, when PMN were stimulated by conditions including those present naturally in the human colonic lumen, monolayers responded with a bumetanide-sensitive short circuit current (Isc) indicative of Cl- secretion, the basis of secretory diarrhea. This Isc response was induced by a neutrophil-derived secretagogue (NDS), which was only active when applied to the luminal surface of monolayers and did not require PMN-epithelial contact. NDS activity is resistant to boiling, acid, and trypsin and passes a 500 nominal mol wt cutoff filter. NDS activity is not secondary to the respiratory burst products O2- or H2O2 and does not appear to be a myeloperoxidase product. We speculate NDS elicited Cl- secretion may contribute to the secretory diarrhea seen in patients with intestinal inflammation and crypt abscesses.
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: S
authors.initials: S
authors.lastname: Nash
authors.forename: C
authors.initials: C
authors.lastname: Parkos
authors.forename: A
authors.initials: A
authors.lastname: Nusrat
authors.forename: C
authors.initials: C
authors.lastname: Delp
authors.forename: J L
authors.initials: JL
authors.lastname: Madara
mesh_terms: D000038:Abscess / Q000503:physiopathology*; D002034:Bumetanide / Q000494:pharmacology; D002463:Cell Membrane Permeability; D004553:Electric Conductivity; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D066298:In Vitro Techniques; D007410:Intestinal Diseases / Q000503:physiopathology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008954:Models, Biological; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D008070:Lipopolysaccharides; D002034:Bumetanide; D009240:N-Formylmethionine Leucyl-Phenylalanine; D006861:Hydrogen Peroxide; D013755:Tetradecanoylphorbol Acetate