Ozone (O3), a photochemical oxidant pollutant, produces lung inflammation, alters lung function, and may disrupt normal host defense mechanisms upon inhalation in humans and other animal species. In vivo O3 exposure has been reported to alter the lung metabolism of arachidonic acid (AA). The metabolites of AA are potent autocoids which can regulate numerous biological functions. Alveolar macrophages (AM) are a potentially rich source of AA metabolites in the lung and in vivo O3 exposure has been reported to alter some AM functions. The effects of in vitro ozone exposure upon AM may indicate if this cell type has an altered AA metabolism in response to in vivo oxidant exposure.. Changes in the synthesis of AM arachidonate products may play a role in the altered immune, inflammatory, and physiological processed observed upon O3 inhalation. Characterization of the changes in human AM arachidonate metabolism induced by an acute or chronic in vitro O3 exposure (0.1-1.0 ppm) will be accomplished by examining media supernatants of O3-exposed AM for AA metabolites by a combination of high performance liquid chromatography (HPLC), thin layer chromatography, and radioimmunoassay. The mechanisms responsible for the O3-induced changes in AA metabolism will be determined. The involvement of hydrogen peroxide (H2O2) in AM arachidonate metabolism induced by an acute exposure will be examined by use of an intracellular fluorescent indicator of H2O2 presence. Effects on AA metabolism induced by chronic exposure will be examined through molecular biological techniques measuring the amount of cyclooxygenase protein present. The biological effects of an unidentified compound(s) (""""""""peak 1"""""""". isolated by HPLC), derived from AA and released by AM in response to O3 exposure, on the functions of cultured lung immune cell types (neutrophils, lymphocytes, and AM) in bioassay systems will be determined. Additionally bronchoalveolar lavage fluid of humans exposed in vivo to O3 will be analyzed by HPLC in order to determine if peak 1 is released into the lungs during exposure.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
1R01ES004951-01
Application #
3253128
Study Section
Toxicology Study Section (TOX)
Project Start
1989-08-01
Project End
1994-07-31
Budget Start
1989-08-01
Budget End
1990-07-31
Support Year
1
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Type
Schools of Medicine
DUNS #
078861598
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
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