Arachidonic acid metabolism in silica-stimulated bovine alveolar macrophages
The in vitro production of arachidonic acid (AA) metabolites in adherent bovine alveolar macrophages (BAM) incubated with silica was investigated. BAM were pre-labelled with {sup 3}H-AA, and lipid metabolites released into the culture medium were analyzed by high performance liquid chromatography (HPLC). Lactate dehydrogenase (LDH) release was simultaneously assayed to provide an indication of cell injury. Increasing doses of silica selectively stimulated the 5-lipoxygenase pathway of AA metabolism, while cyclooxygenase metabolite output was suppressed. LDH release increased in a linear, dose-dependent fashion over the range of silica doses used. Moreover, within 15 min following addition of a high silica dose, a shift to the production of 5-lipoxygenase metabolites occurred, accompanied by a reduction in cyclooxygenase products. This rapid alteration in AA metabolism preceded cell injury. To examine the relationship between cytotoxicity and AA metabolite release by BAM exposed to silicas with different cytotoxic and fibrogenic activities, BAM were exposed to different doses of DQ-12, Minusil-5, and Sigma silicas, and carbonyl iron beads. The median effective dose (ED{sub 50}) of each particulate to stimulate the release of AA metabolites and LDH was calculated. The ED{sub 50} values for DQ-12, Minusil-5, and Sigma silica showed that the relative cytotoxicities of the different silicas for BAM corresponded to the relative potencies of the silicas to elicit 5-lipoxygenase metabolites from BAM. These results indicate that the cytotoxic, and presumed fibrogenic potential, of a silica is correlated with the potency to stimulate the release of leukotrienes from AM.
- Research Organization:
- Washington State Univ., Pullman, WA (USA)
- OSTI ID:
- 5526637
- Resource Relation:
- Other Information: Thesis (Ph. D.)
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
ARACHIDONIC ACID
METABOLISM
SILICA
BIOLOGICAL EFFECTS
BIOLOGICAL PATHWAYS
IN VITRO
LACTATE DEHYDROGENASE
LIQUID COLUMN CHROMATOGRAPHY
LUNGS
MACROPHAGES
METABOLITES
OXYGENASES
TRACER TECHNIQUES
TRITIUM COMPOUNDS
ANIMAL CELLS
BODY
CARBOXYLIC ACIDS
CHALCOGENIDES
CHROMATOGRAPHY
CONNECTIVE TISSUE CELLS
ENZYMES
HEMIACETAL DEHYDROGENASES
HYDROGEN COMPOUNDS
ISOTOPE APPLICATIONS
MINERALS
MONOCARBOXYLIC ACIDS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
OXIDE MINERALS
OXIDES
OXIDOREDUCTASES
OXYGEN COMPOUNDS
PHAGOCYTES
RESPIRATORY SYSTEM
SEPARATION PROCESSES
SILICON COMPOUNDS
SILICON OXIDES
SOMATIC CELLS
550501* - Metabolism- Tracer Techniques