title: Neutrophil apoptosis is delayed in patients with inflammatory bowel disease.
abstract: Delayed neutrophil apoptosis is a feature of persistent acute inflammation. Neutrophil-mediated damage has been shown to be associated with the development of inflammatory bowel disease (IBD). Persistence of these cells both at the colonic site and circulation may further contribute to IBD. The aims of this study were to determine whether neutrophils isolated from IBD patients delay apoptosis and to investigate possible mechanisms involved in this delay. We studied 20 patients with IBD, 13 with Crohn's disease, and 7 with ulcerative colitis, all of whom were undergoing intestinal resection for symptomatic disease. Seventeen patients undergoing elective resection of colon cancer acted as operative controls. Systemic, mesenteric arterial, and mesenteric venous blood was harvested. Neutrophils isolated from patients with IBD showed decreased spontaneous apoptosis compared to cancer patients. Mesenteric venous serum of IBD patients contributed to this delay, which contained higher concentrations of interleukin-8 (IL-8). Pro-caspase 3 expression was also reduced in IBD neutrophils, which may contribute to decreased spontaneous and Fas antibody-induced apoptosis. Neutrophil apoptosis may be altered in Crohn's disease and ulcerative colitis through release of anti-apoptotic cytokines and altered caspase expression. The alterations in cell death mechanisms may lead to persistence of the inflammatory response associated with IBD.
authors.affiliation: Department of Surgery, University College Dublin, Mater Misericordiae Hospital, Ireland.
authors.forename: A E
authors.initials: AE
authors.lastname: Brannigan
authors.forename: P R
authors.initials: PR
authors.lastname: O'Connell
authors.forename: H
authors.initials: H
authors.lastname: Hurley
authors.forename: A
authors.initials: A
authors.lastname: O'Neill
authors.forename: H R
authors.initials: HR
authors.lastname: Brady
authors.forename: J M
authors.initials: JM
authors.lastname: Fitzpatrick
authors.forename: R W
authors.initials: RW
authors.lastname: Watson
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000187:drug effects; D016022:Case-Control Studies; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000097:blood; D003093:Colitis, Ulcerative / Q000201:enzymology / Q000276:immunology / Q000473:pathology*; D003424:Crohn Disease / Q000201:enzymology / Q000276:immunology / Q000473:pathology*; D004792:Enzyme Precursors / Q000097:blood; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000494:pharmacology; D066298:In Vitro Techniques; D016209:Interleukin-8 / Q000097:blood / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects / Q000473:pathology*
chemical_list: D004792:Enzyme Precursors; D016209:Interleukin-8; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases; D006854:Hydrocortisone