title: Neutrophil migration into indomethacin induced rat small intestinal injury is CD11a/CD18 and CD11b/CD18 co-dependent.
abstract: BACKGROUND
  Neutrophils may exacerbate intestinal inflammatory diseases through secretion of proteolytic enzymes and reactive oxygen and nitrogen intermediates.
  
  
  OBJECTIVE
  To define the mechanisms involved in neutrophil infiltration into the non-steroidal anti-inflammatory disease inflamed intestine to develop strategies to regulate this process.
  
  
  METHODS
  The small intestinal epithelium of (15 mg/kg) indomethacin treated rats was examined for cytokine mRNA. The kinetics of neutrophil accumulation into the gastrointestinal tract (including lumen contents) of inflamed rats was determined using radiolabelled (111In) neutrophils injected intravenously followed by a three hour migration period. To determine which adhesion molecules were critical for migration, rats were also injected with function blocking monoclonal antibodies to the beta2 (CD11/CD18) integrins.
  
  
  RESULTS
  Interleukin 1beta, interleukin 1 receptor II, tumour necrosis factor alpha, and monocyte inflammatory peptide 2 but not monocyte chemoattractant protein 1 mRNA were detected in the epithelium within hours of indomethacin injection. Neutrophils were detectable in the small intestine and intestinal lumen by six hours and continued to accumulate until 48 hours post indomethacin injection. Neutrophil accumulation in the intestine was essentially blocked by anti-CD18, and partially blocked by either anti-CD11a or CD11b antibody treatment. Migration into the intestinal lumen was reduced by anti-CD11b.
  
  
  CONCLUSIONS
  The small intestinal epithelium acts as one source of cytokines with properties important in the recruitment of neutrophils. In turn, neutrophil migration into the indomethacin inflamed small intestine is mediated by CD11a/CD18 and CD11b/CD18.
authors.affiliation: Dalhousie Inflammation Group and Department of Pediatrics, and Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada. Andrew.Stadnyk@Dal.Ca
authors.forename: A W
authors.initials: AW
authors.lastname: Stadnyk
authors.forename: C
authors.initials: C
authors.lastname: Dollard
authors.forename: T B
authors.initials: TB
authors.lastname: Issekutz
authors.forename: A C
authors.initials: AC
authors.lastname: Issekutz
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000911:Antibodies, Monoclonal / Q000276:immunology; D002465:Cell Movement; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D004751:Enteritis / Q000139:chemically induced / Q000276:immunology*; D004847:Epithelial Cells / Q000276:immunology; D005786:Gene Expression Regulation / Q000187:drug effects; D007213:Indomethacin; D007413:Intestinal Mucosa / Q000276:immunology; D007421:Intestine, Small / Q000276:immunology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology*; D016177:Macrophage-1 Antigen / Q000276:immunology*; D008297:Male; D020556:Neutrophil Infiltration / Q000187:drug effects / Q000276:immunology*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011917:Rats, Inbred Lew
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000911:Antibodies, Monoclonal; D016207:Cytokines; D016169:Lymphocyte Function-Associated Antigen-1; D016177:Macrophage-1 Antigen; D012333:RNA, Messenger; D007213:Indomethacin