Ozone-induced alterations in arachidonic acid metabolism in cultured lung cell types

Thesis/Dissertation · Wed Jan 01 00:00:00 EST 1986

OSTI ID:6855397

Madden, M C

One of the most sensitive cells to ozone (O/sub 3/) damage is the pulmonary endothelial cell which may mediate the response of the lung to injury by productions of the autacoid prostacyclin (PGl/sub 2/), a metabolite of arachidonic acid. Exposure of endothelial cell cultures to ozone produced a concentration dependent decreases in the synthesis of PGl/sub 2/. Release of /sup 3/H-arachidonic acid from endothelial cells was increased after two hours of 0.3 and 1.0 ppm O/sub 3/ exposure while incubation of cells with 20 ..mu..M and arachidonate (4 min) after exposure resulted in a decreased PGl/sub 2/ synthesis. Cells exposed to 1.0 ppm O/sub 3/ did not have a decreased PGl/sub 2/ production when incubated with 5 ..mu..M PGH/sub 2/ immediately after exposure. These results are consistent with an O/sub 3/-induced inhibition of cyclooxygenase activity. O/sub 3/ exposure (1.0 ppm) produced a rapid decrease in endothelial PGl/sub 2/ synthesis. The data suggest that cyclooxygenase was not inactivated by increased autooxidation due to metabolism of increased free arachidonate. PGl/sub 2/ synthesis returned to control amounts within 12 hours after ozone exposure similar to the recovery time of irreversibly inhibited cyclooxygenase suggesting that recovery was due to de novo synthesis of enzyme. Lipid peroxides and/or hydrogen peroxide (H/sub 2/O/sub 2/) may have caused the inhibition of cyclooxygenase. Incubation of cells with catalase (5 U/ml) protected against the O/sub 3/-induced depression in PGl/sub 2/ synthesis. Exogenously added H/sub 2/O/sub 2/ (greater than or equal to 75 ..mu..M) caused a stimulation of basal PGl/sub 2/ production but depressed arachidonate-stimulated synthesis. O/sub 3/ exposure (2 hr, 1.0 ppm) produced altered metabolism of arachidonate in other important lung cell types, e.g., a decreased PGl/sub 2/ synthesis in smooth muscle cultures. Exposure of lung macrophages to O/sub 3/ caused an increase in almost all arachidonate metabolites produced.

• Research Organization: North Carolina Univ., Chapel Hill (USA)
• OSTI ID: 6855397
• Resource Relation: Other Information: Thesis (Ph. D.)
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ARACHIDONIC ACID
METABOLISM
OZONE
TOXICITY
ANIMAL CELLS
BIOSYNTHESIS
DOSE-RESPONSE RELATIONSHIPS
ENDOTHELIUM
ENZYME ACTIVITY
HYDROGEN PEROXIDE
INHIBITION
LIPIDS
LUNGS
MACROPHAGES
METABOLITES
MUSCLES
OXYGENASES
PEROXIDES
TRACER TECHNIQUES
TRITIUM COMPOUNDS
ANIMAL TISSUES
BODY
CARBOXYLIC ACIDS
CONNECTIVE TISSUE CELLS
ENZYMES
HYDROGEN COMPOUNDS
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MONOCARBOXYLIC ACIDS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
OXIDOREDUCTASES
OXYGEN COMPOUNDS
PHAGOCYTES
RESPIRATORY SYSTEM
SOMATIC CELLS
SYNTHESIS
TISSUES
560300* - Chemicals Metabolism & Toxicology