Ozone-induced alteration in beta-adrenergic pharmacological modulation of pulmonary macrophages.
Ozone is a ubiquitous air pollutant which can affect numerous function s of the respiratory system. However, previous work has not provided any information concerning its ability to modulate pharmacological receptors of pulmonary macrophages. This study examined, using a chemiluminescence assay, the beta-adrenergic modulation of pulmonary macrophages harvested from rabbits exposed for 3 hr/day for 5 days to 0.1, 0.3 or 0.6 ppm ozone (O3) or to 3 hr/day for 20 days to 0.1 or 0.3 ppm. Receptor activity was monitored using release of reactive oxygen species (ROS) following administration to the cells of the beta2-receptor agonist, isoproterenol. An O3-exposure concentration-dependent response was observed for isoproterenol efficacy following 5-day exposures, in that 0.1 ppm O3 induced a significant enhancement of beta-adrenergic inhibition of ROS production, 0.3 ppm ozone produced no significant change from control, and 0.6 ppm decreased inhibition. No significant effects on beta-adrenergic modulation were noted following the 20-day exposures. The results of this study suggest that short-term repeated exposures to O3 are capable of inducing alterations in the pharmacological functioning of pulmonary macrophages, while longer term exposures may result in adaptation. Alterations in receptor function have implications in terms of pulmonary defense and disease.
McGovern
T J
TJ
Institute of Environmental Medicine, New York University Meidcal Center, Tuxedo, New York 10987, USA.
el-Fawal
H A
HA
Chen
L C
LC
Schlesinger
R B
RB
D000318:Adrenergic beta-Agonists / Q000378:metabolism / Q000494:pharmacology*; D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D018893:Bronchoalveolar Lavage; D002478:Cells, Cultured; D007545:Isoproterenol / Q000494:pharmacology; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010083:Oxidants, Photochemical / Q000633:toxicity*; D010126:Ozone / Q000633:toxicity*; D011817:Rabbits; D017382:Reactive Oxygen Species / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D016897:Respiratory Burst / Q000187:drug effects; D012680:Sensitivity and Specificity; D013047:Specific Pathogen-Free Organisms
D000318:Adrenergic beta-Agonists; D000393:Air Pollutants; D010083:Oxidants, Photochemical; D017382:Reactive Oxygen Species; D011943:Receptors, Adrenergic, beta; D010126:Ozone; D007545:Isoproterenol