The effect of platelet activating factor antagonist on ozone-induced airway inflammation and bronchial hyperresponsiveness in guinea pigs

Journal Article · Thu Oct 01 04:00:00 EDT 1992 · American Review of Respiratory Disease (New York); (United States)

DOI:https://doi.org/10.1164/ajrccm/146.4.916· OSTI ID:6968022

Tan, W C; Bethel, R A ^[1]

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1. Department of Medicine, National University of Singapore (Singapore)

We investigated the role of platelet-activating factor (PAF) in ozone-induced airway responses by examining the effects of L659,989, a potent PAF antagonist, on bronchial hyperresponsiveness and airway inflammation. Twenty-four male guinea pigs were studied in four equal groups. Total lung resistance (RL) in intubated and spontaneously breathing animals was measured in a constant-volume body plethysmograph. Dose-response curves to methacholine were determined in all animals at the start of the experiment. These were repeated on a separate day after the following types of treatments: air exposure in Group 1, intraperitoneally administered alcohol and air exposure in Group 2; intraperitoneally administered alcohol and ozone exposure in Group 3, and intraperitoneally administered L659,989 (a specific PAF antagonist), 5 mg/kg dissolved in alcohol, and ozone exposure in Group 4. Bronchoalveolar lavage (BAL) was performed after the second methacholine challenge, and the bronchial mucosa was also examined for inflammatory cells. Exposure to 3 ppm ozone for 2 h resulted in a three-doubling concentration increase in bronchial responsiveness, which was not significantly inhibited by prior treatment with L659,989. Ozone induced a 1.8-fold increase in BAL total cell count, increased eosinophilic influx into the airways, and increased eosinophilic infiltration in the bronchial mucosa, which were all not inhibited by L659,989 pretreatment. The results suggest that PAF may not have an essential role in ozone-induced airway hyperresponsiveness and nonallergic airway inflammation.

• OSTI ID: 6968022
• Journal Information: American Review of Respiratory Disease (New York); (United States), Journal Name: American Review of Respiratory Disease (New York); (United States) Vol. 146:4; ISSN ARDSBL; ISSN 0003-0805
• Country of Publication: United States
• Language: English

Related Subjects

560300* -- Chemicals Metabolism & Toxicology
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMALS
BIOLOGICAL FUNCTIONS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BLOOD COAGULATION FACTORS
BODY FLUIDS
COAGULANTS
DOSE-RESPONSE RELATIONSHIPS
DRUGS
EOSINOPHILS
FURANS
GUINEA PIGS
HEMATOLOGIC AGENTS
HETEROCYCLIC COMPOUNDS
LAVAGE
LEUKOCYTES
MAMMALS
MATERIALS
ORGANIC COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
OZONE
PROTEINS
RESPIRATORY SYSTEM
RODENTS
SENSITIVITY
TOXICITY
VERTEBRATES