Effect of an anti-Mo1 MAb on ozone-induced airway inflammation and airway hyperresponsiveness in dogs.
Ozone inhalation causes neutrophil migration into the airway and airway hyperresponsiveness in dogs. The leukocyte adhesion molecule Mo1 (CD11b/CD18) is a heterodimeric glycoprotein the expression of which is necessary for neutrophil adhesion to endothelium. To evaluate the contribution of Mo1 to ozone-induced neutrophil influx and airway hyperresponsiveness, six dogs were treated intravenously with an Anti-Mo1 monoclonal antibody (3.75 mg/kg in normal saline) that binds to both human and canine Mo1, or the diluent alone, 1.5 h before inhaling ozone (3 ppm for 30 min), or dry air. Airway responses to doubling doses of inhaled acetylcholine (ACh) were measured before and after inhalation of ozone. Neutrophil influx was assessed by bronchoalveolar lavage (BAL) performed after the second ACh inhalation. Treatment with anti-Mo1 prevented the ozone-induced influx of neutrophils into BAL. After diluent and inhaled dry air, the neutrophil count in BAL was 1.49 +/- 1.26 (SE) x 10(4) (5.0% of total cells). After diluent and inhaled ozone, the neutrophil count increased to 7.27 +/- 3.22 (SE) x 10(4) (22.6% of total cells) (P < 0.05). After anti-Mo1 and inhaled ozone, the neutrophil count was 1.48 +/- 0.62 (SE) x 10(4) (8.5% of total cells). Treatment with anti-Mo1 also significantly reduced the number of eosinophils in BAL after ozone. Ozone-induced ACh airway hyperresponsiveness was not prevented by treatment with anti-Mo1. These results indicate that expression of Mo1 is necessary for ozone-induced neutrophil migration into the airway lumen.
Li
Z
Z
Department of Biomedical Science, McMaster University, Hamilton, Ontario, Canada.
Daniel
E E
EE
Lane
C G
CG
Arnaout
M A
MA
O'Byrne
P M
PM
D000109:Acetylcholine / Q000494:pharmacology; D000280:Administration, Inhalation; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid / Q000473:pathology; D002634:Chemotaxis, Leukocyte; D004285:Dogs; D007249:Inflammation / Q000139:chemically induced / Q000473:pathology; D016177:Macrophage-1 Antigen / Q000276:immunology*; D009504:Neutrophils / Q000473:pathology / Q000502:physiology; D010126:Ozone; D012130:Respiratory Hypersensitivity / Q000139:chemically induced*; D012140:Respiratory Tract Diseases / Q000139:chemically induced* / Q000473:pathology
D000911:Antibodies, Monoclonal; D016177:Macrophage-1 Antigen; D010126:Ozone; D000109:Acetylcholine