Antagonism of ICAM-1 attenuates airway and tissue responses to antigen in sensitized rats.
Airway inflammation is involved in the pathogenesis of bronchial asthma. Intercellular adhesion molecule-1 (ICAM-1) is a ligand for lymphocyte function-associated antigen-1 alpha (LFA-1 alpha) and has been shown to be required for leukocyte migration into inflamed area. The purpose of this report was to investigate the role of ICAM-1/LFA-1 alpha pathway in a rat model of extrinsic asthma using monoclonal antibodies (mAbs). We chose to study ovalbumin (OA)-sensitized Brown-Norway rats, an animal model in which there is a high prevalence of both early (ER) and late responses (LR) after antigen challenge. We measured tracheal and alveolar pressure using alveolar capsules in open-chested, mechanically ventilated animals to calculate resistance of lung (RL), tissue (Rti), and airway (Raw). In the OA group, both ER (RL, Rti, Raw = 263 +/- 16, 235 +/- 10, 309 +/- 38% baseline) and LR (RL, Rti, Raw = 265 +/- 26, 238 +/- 13, 316 +/- 55% baseline) were observed. The administration of mAbs to ICAM-1 and LFA-1 alpha significantly attenuated the ER (RL, Rti, Raw = 146 +/- 9, 141 +/- 11, 156 +/- 8% baseline) and LR (RL, Rti, Raw = 128 +/- 8, 124 +/- 5, 137 +/- 1% baseline), indicating that both airway and lung tissues were involved in this mechanism. The current observations suggest that ICAM-1/LFA-1 alpha pathway is involved in both the early and late responses in a rat model of allergic asthma. The antagonism of ICAM-1 and LFA-1 alpha may provide a potential therapeutic approach to the early and late responses of bronchial asthma.
Nagase
T
T
Department of Geriatrics, Faculty of Medicine, University of Tokyo, Japan.
Fukuchi
Y
Y
Matsuse
T
T
Sudo
E
E
Matsui
H
H
Orimo
H
H
D000403:Airway Resistance; D000818:Animals; D000911:Antibodies, Monoclonal; D001249:Asthma / Q000503:physiopathology*; D001980:Bronchi / Q000503:physiopathology*; D001985:Bronchial Provocation Tests; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology*; D008168:Lung / Q000503:physiopathology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology*; D051381:Rats; D011914:Rats, Inbred BN; D013997:Time Factors
D000911:Antibodies, Monoclonal; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1