Endothelial leukocyte adhesion molecule-1 mediates antigen-induced acute airway inflammation and late-phase airway obstruction in monkeys

• Published in: The Journal of clinical investigation 1991-10, Vol.88 (4), p.1407-1411
• Main Authors: GUNDEL, R. H, WAGNER, C. D, TORCELLINI, C. A, CLARKE, C. C, HAYNES, N, ROTHLEIN, R, SMITH, C. W, LETTS, L. G
• Format: Article
• Language: English
• Subjects: Acute Disease; Airway Obstruction - etiology; Animals; Antibodies, Monoclonal - immunology; Antigens - immunology; Biological and medical sciences; Bronchitis - etiology; Cell Adhesion Molecules - analysis; Cell Adhesion Molecules - physiology; E-Selectin; Eosinophils - physiology; Macaca fascicularis; Male; Medical sciences; Neutrophils - physiology; Pneumology
• ISSN: 0021-9738; 1558-8238
• DOI: 10.1172/jci115447

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.