title: Endothelial leukocyte adhesion molecule-1 mediates antigen-induced acute airway inflammation and late-phase airway obstruction in monkeys.
abstract: This study examines the role of endothelial leukocyte adhesion molecule-1 (ELAM-1) in the development of the acute airway inflammation (cell influx) and late-phase airway obstruction in a primate model of extrinsic asthma. In animals sensitive to antigen, a single inhalation exposure induced the rapid expression of ELAM-1 (6 h) exclusively on vascular endothelium that correlated with the influx of neutrophils into the lungs and the onset of late-phase airway obstruction. In contrast, basal levels of ICAM-1 was constitutively expressed on vascular endothelium and airway epithelium before antigen challenge. After the single antigen exposure, changes in ICAM-1 expression did not correlate with neutrophil influx or the change in airway caliber. This was confirmed by showing that pretreatment with a monoclonal antibody to ICAM-1 did not inhibit the acute influx of neutrophils associated with late-phase airway obstruction, whereas a monoclonal antibody to ELAM-1 blocked both the influx of neutrophils and the late-phase airway obstruction. This study demonstrates a functional role for ELAM-1 in the development of acute airway inflammation in vivo. We conclude that, in primates, the late-phase response is the result of an ELAM-1 dependent influx of neutrophils. Therefore, the regulation of ELAM-1 expression may provide a novel approach to controlling the acute inflammatory response, and thereby, affecting airway function associated with inflammatory disorders, including asthma.
authors.affiliation: Department of Pharmacology, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut 06877.
authors.forename: R H
authors.initials: RH
authors.lastname: Gundel
authors.forename: C D
authors.initials: CD
authors.lastname: Wegner
authors.forename: C A
authors.initials: CA
authors.lastname: Torcellini
authors.forename: C C
authors.initials: CC
authors.lastname: Clarke
authors.forename: N
authors.initials: N
authors.lastname: Haynes
authors.forename: R
authors.initials: R
authors.lastname: Rothlein
authors.forename: C W
authors.initials: CW
authors.lastname: Smith
authors.forename: L G
authors.initials: LG
authors.lastname: Letts
mesh_terms: D000208:Acute Disease; D000402:Airway Obstruction / Q000209:etiology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000941:Antigens / Q000276:immunology*; D001991:Bronchitis / Q000209:etiology*; D015815:Cell Adhesion Molecules / Q000032:analysis / Q000502:physiology*; D019040:E-Selectin; D004804:Eosinophils / Q000502:physiology; D008252:Macaca fascicularis; D008297:Male; D009504:Neutrophils / Q000502:physiology
chemical_list: D000911:Antibodies, Monoclonal; D000941:Antigens; D015815:Cell Adhesion Molecules; D019040:E-Selectin