Antioxidant transport modulates peripheral airway reactivity and inflammation during ozone exposure.
We examined the effects of ozone (O(3)) and endogenous antioxidant transport on canine peripheral airway function, central airway function, epithelial integrity, and inflammation. Dogs were either untreated or pretreated with probenecid (an anion-transport inhibitor) and exposed for 6 h to 0.2 parts/million O(3). Peripheral airway resistance (Rpa) and reactivity (DeltaRpa) were monitored in three sublobar locations before and after exposure to either air or O(3). Pulmonary resistance and transepithelial potential difference in trachea and bronchus were also recorded. Bronchoalveolar lavage fluid (BALF) was collected before, during, and after exposure. O(3) increased Rpa and DeltaRpa only in probenecid-treated dogs and in a location-dependent fashion. Pulmonary resistance and potential difference in bronchus increased after O(3) exposure regardless of treatment. O(3) markedly increased BALF neutrophils only in untreated dogs. With the exception of hexanal, O(3) did not alter any BALF constituent examined. Probenecid reduced BALF ascorbate, BALF protein, and plasma urate. We conclude that 1) a 6-h exposure to 0.2 parts/million O(3) represents a subthreshold stimulus in relation to its effects on peripheral airway function in dogs, 2) antioxidant transport contributes to the maintenance of normal airway tone and reactivity under conditions of oxidant stress, 3) O(3)-induced changes in Rpa and DeltaRpa are dependent on location, and 4) peripheral airway hyperreactivity and inflammation reflect independent responses to O(3) exposure. Finally, although anion transport mitigates the effect of O(3) on peripheral airway function, it contributes to the development of airway inflammation and may represent a possible target for anti-inflammatory prevention or therapy.
Freed
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Department of Environmental Health Sciences, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21205, USA. afreed@jhsph.edu
Cueto
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Pryor
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D000403:Airway Resistance / Q000187:drug effects; D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001205:Ascorbic Acid / Q000494:pharmacology; D001693:Biological Transport, Active / Q000187:drug effects; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002452:Cell Count; D002839:Chromans / Q000494:pharmacology; D004285:Dogs; D007249:Inflammation / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D010083:Oxidants, Photochemical / Q000633:toxicity*; D010126:Ozone / Q000633:toxicity*; D010545:Peroxides / Q000378:metabolism; D011339:Probenecid / Q000494:pharmacology; D011506:Proteins / Q000378:metabolism; D012137:Respiratory System / Q000187:drug effects* / Q000473:pathology; D014528:Uricosuric Agents / Q000494:pharmacology
D000447:Aldehydes; D000975:Antioxidants; D002839:Chromans; D010083:Oxidants, Photochemical; D010545:Peroxides; D011506:Proteins; D014528:Uricosuric Agents; D010126:Ozone; D011339:Probenecid; D001205:Ascorbic Acid; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid