Effect of an anti-Mo1 MAb on ozone-induced airway inflammation and airway hyperresponsiveness in dogs
- McMaster Univ., Hamilton, Ontario (Canada)
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.
- OSTI ID:
- 6750547
- Journal Information:
- American Journal of Physiology; (United States), Vol. 263:6 Pt 1; ISSN 0002-9513
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
BRONCHI
SENSITIVITY
DOGS
RESPIRATORY SYSTEM DISEASES
NEUTROPHILS
ADHESION
MIGRATION
OZONE
INHALATION
ACETYLCHOLINE
ANTIBODIES
ENDOTHELIUM
EOSINOPHILS
INFLAMMATION
LAVAGE
AMINES
AMMONIUM COMPOUNDS
ANIMAL TISSUES
ANIMALS
AUTONOMIC NERVOUS SYSTEM AGENTS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY
BODY FLUIDS
DISEASES
DRUGS
ESTERS
INTAKE
LEUKOCYTES
MAMMALS
MATERIALS
NEUROREGULATORS
ORGANIC COMPOUNDS
PARASYMPATHOMIMETICS
PATHOLOGICAL CHANGES
QUATERNARY COMPOUNDS
RESPIRATORY SYSTEM
SYMPTOMS
TISSUES
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology
550900 - Pathology
550200 - Biochemistry