OZONE EFFECTS ON AIRWAY RESPONSIVENESS, LUNG INJURY, AND INFLAMMATION. COMPARATIVE RAT STRAIN AND IN VIVO/IN VITRO INVESTIGATIONS

Asthmatic individuals appear to be particularly sensitive to the effects of certain air pollutants-including ozone (O3), an oxidant ambient air pollutant-for reasons that are poorly understood. The general purpose of these studies, therefore, was to expand and improve upon toxicologic methods for as...

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Bibliographic Details
Published in:Inhalation toxicology 1999-11, Vol.11 (11), p.1015-1040
Main Authors: Janice, A. Dye, Madden, Michael C, Judy, H. Richards, James, R. Lehmann, Robert, B. Devlin, Daniel, L. Costa
Format: Article
Language:English
Subjects:
Animals
Bronchial Hyperreactivity - chemically induced
Bronchial Hyperreactivity - pathology
Bronchial Provocation Tests
Bronchoalveolar Lavage Fluid - cytology
Culture Techniques
Epithelium - pathology
Inhalation Exposure - adverse effects
Lung Diseases - chemically induced
Lung Diseases - pathology
Male
Oxidants, Photochemical - toxicity
Ozone - toxicity
Pneumonia - chemically induced
Pneumonia - pathology
Rats
Rats, Inbred F344
Rats, Sprague-Dawley
Rats, Wistar
Respiratory Physiological Phenomena - drug effects
Species Specificity
Trachea - pathology
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Summary:Asthmatic individuals appear to be particularly sensitive to the effects of certain air pollutants-including ozone (O3), an oxidant ambient air pollutant-for reasons that are poorly understood. The general purpose of these studies, therefore, was to expand and improve upon toxicologic methods for assessing ozone-induced effects on the airways of the rat by (1) developing an in vivo testing procedure that allows detection of airway responsiveness changes in rats exposed to ozone; (2) identifying a strain of rat that may be inherently more sensitive to the effects of ozone; and (3) validation of an in vitro epithelial culture system to more directly assess airway cellular/subcellular effects of ozone. Using methacholine inhalation challenges, we detected increased airway responsiveness in senescent F344 rats acutely after ozone exposure (2 ppm 2 h). We also determined that acutely after ozone exposure (0.5 ppm 8 h), Wistar rats developed significantly greater lung injury, neutrophilic inflammation, and bronchoalveolar lavage (BAL) fluid concentrations of IL-6 than either Sprague-Dawley (SD) or F344 rats. SD rats had greater BAL fluid concentrations of prostaglandin E2 (PGE2), while F344 rats consistently exhibited the least effect. Wistar rat-derived tracheal epithelial (RTE) cultures were exposed in vitro to air or ozone (0.1-1.0 ppm 1 h), and examined for analogous effects. In a concentration-dependent manner, ozone exposure resulted in acute but minor cytotoxicity. RT polymerase chain reaction (PCR) analysis of RNA isolated from ozone-exposed cells demonstrated variable increases in steady-state gene expression of IL-6 at 4 h postexposure, while at 24 h cellular fibronectin expression (EIIIA domain) was decreased. Exposure was without effect on macrophage inflammatory protein 2 (MIP-2) or-glutamyl cysteine synthetase expression. At 6 h postexposure, IL-6 synthesis and apical release appeared increased in ozone-exposed cells (1 ppm 1 h). MIP-2 release was not significantly increased in ozone-exposed cells. At 2 h postexposure, ozone exposure resulted in minor increases in apical fibronectin, but exposure was without effect on basolateral accumulation of fibronectin. Exposure to 1.0, but not 0.1 ppm (1 h), increased production of cyclooxygenase (i.e., PGE2) and noncyclooxygenase products of arachidonic acid. Results demonstrate that multiple inflammatory mediator pathways are affected by ozone exposure. Such effects could exacerbate morbidity in individuals
ISSN:0895-8378
1091-7691
DOI:10.1080/089583799196664