title: Role of intercellular adhesion molecule 1 in indomethacin-induced ileitis.
abstract: Adhesion molecules have been implicated in the pathogenesis of inflammatory bowel diseases. We investigated their expression and contribution to leukocyte recruitment in experimental intestinal inflammation. Ileitis was induced in Sprague-Dawley rats by two injections of indomethacin (7.5 mg/kg), given 24 h apart. Endothelial intercellular adhesion molecule-1 (ICAM-1) expression was quantified using the dual radiolabeled monoclonal antibody technique and Mac-1 (CD11b/CD18) expression on leukocytes by flow cytometry. Leukocyte infiltration was monitored by tissue myeloperoxidase (MPO) activity. The first indomethacin injection induced a time- and site-dependent increase of ICAM-1 expression in ileal mucosa and muscularis. The second injection resulted in a reduction of ICAM-1 expression below constitutive levels whereas Mac-1 was upregulated. MPO changes paralleled lesion development over 48 h. ICAM-1 and MPO values were correlated for the first 24 h. Immunoneutralization of either ICAM-1 or Mac-1 attenuated mucosal injury. We conclude that (i) indomethacin-induced ileitis is associated with a temporally disassociated upregulation of ICAM-1 and (ii) despite a reduction in ICAM-1 after 24 h, ICAM-1, in concert with Mac-1, contributes to mucosal injury and leukocyte infiltration elicited by indomethacin.
authors.affiliation: Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71130-3932, USA.
authors.forename: C F
authors.initials: CF
authors.lastname: Krieglstein
authors.forename: J W
authors.initials: JW
authors.lastname: Salter
authors.forename: W H
authors.initials: WH
authors.lastname: Cerwinka
authors.forename: J M
authors.initials: JM
authors.lastname: Russell
authors.forename: G
authors.initials: G
authors.lastname: Schuermann
authors.forename: M
authors.initials: M
authors.lastname: Bruewer
authors.forename: F S
authors.initials: FS
authors.lastname: Laroux
authors.forename: M B
authors.initials: MB
authors.lastname: Grisham
authors.forename: D N
authors.initials: DN
authors.lastname: Granger
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D004195:Disease Models, Animal; D004727:Endothelium / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D007079:Ileitis / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology*; D007213:Indomethacin / Q000633:toxicity*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D007962:Leukocytes / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D016177:Macrophage-1 Antigen / Q000378:metabolism; D008297:Male; D009500:Neutralization Tests; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000911:Antibodies, Monoclonal; D016177:Macrophage-1 Antigen; D018799:Intercellular Adhesion Molecule-1; D009195:Peroxidase; D007213:Indomethacin