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 #
5R01ES004951-04
Application #
3253133
Study Section
Toxicology Subcommittee 2 (TOX)
Project Start
1989-08-01
Project End
1994-07-31
Budget Start
1992-08-01
Budget End
1993-07-31
Support Year
4
Fiscal Year
1992
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
Kozumbo, W J; Hanley, N M; Agarwal, S et al. (1996) Products of ozonized arachidonic acid potentiate the formation of DNA single strand breaks in cultured human lung cells. Environ Mol Mutagen 27:185-95
Devlin, R B; McDonnell, W F; Becker, S et al. (1996) Time-dependent changes of inflammatory mediators in the lungs of humans exposed to 0.4 ppm ozone for 2 hr: a comparison of mediators found in bronchoalveolar lavage fluid 1 and 18 hr after exposure. Toxicol Appl Pharmacol 138:176-85
Hazucha, M J; Madden, M; Pape, G et al. (1996) Effects of cyclo-oxygenase inhibition on ozone-induced respiratory inflammation and lung function changes. Eur J Appl Physiol Occup Physiol 73:17-27
Bromberg, P A; Koren, H S (1995) Ozone-induced human respiratory dysfunction and disease. Toxicol Lett 82-83:307-16
Wright, D T; Adler, K B; Akley, N J et al. (1994) Ozone stimulates release of platelet activating factor and activates phospholipases in guinea pig tracheal epithelial cells in primary culture. Toxicol Appl Pharmacol 127:27-36
Madden, M C; Smith, J P; Dailey, L A et al. (1994) Polarized release of lipid mediators derived from phospholipase A2 activity in a human bronchial cell line. Prostaglandins 48:197-215
McKinnon, K P; Madden, M C; Noah, T L et al. (1993) In vitro ozone exposure increases release of arachidonic acid products from a human bronchial epithelial cell line. Toxicol Appl Pharmacol 118:215-23
Madden, M C; Friedman, M; Hanley, N et al. (1993) Chemical nature and immunotoxicological properties of arachidonic acid degradation products formed by exposure to ozone. Environ Health Perspect 101:154-64
Samet, J M; Friedman, M (1992) Effect of ozone on platelet activating factor metabolism in phorbol-differentiated HL60 cells. Toxicol Appl Pharmacol 117:19-25
Samet, J M; Noah, T L; Devlin, R B et al. (1992) Effect of ozone on platelet-activating factor production in phorbol-differentiated HL60 cells, a human bronchial epithelial cell line (BEAS S6), and primary human bronchial epithelial cells. Am J Respir Cell Mol Biol 7:514-22

Showing the most recent 10 out of 11 publications