Effects of asbestos and silica on superoxide anion production in the guinea pig alveolar macrophage
This study examined the effect of asbestos and silica on the activation pathway of the guinea pig alveolar macrophage. Activation of macrophages by physiological agents results in stimulation of phospholipase C causing phosphatidyl inositol turnover and intracellular calcium mobilization. Phosphatidyl inositol turnover produces diacylglycerol which activates protein kinase C causing superoxide anion production. Chrysotile stimulated alveolar macrophages to produce superoxide anion. This stimulation proceeded via phospholipase C, since chrysotile stimulated phosphatidyl inositol turnover and intracellular calcium mobilization. The possible involvement of a coupling protein was evaluated by pretreating cells with pertussis toxin. Potential binding sites for chrysotile stimulation were examined using a series of nine lectins. Chrysotile-stimulated superoxide anion production was blocked by pretreatment with lectins which bound to mannose, fucose, or N-acetylgalactosamine. In addition, incubation with the N-acetylglucosamine, but not by lectins which bound to mannose, fucose, or N-acetylgalactosamine. In addition, incubation with the N-acetylglucosamine polymer, chitin, inhibited chrysotile-stimulated superoxide anion production, suggesting that chrysotile stimulated superoxide anion production by binding to N-acetylglucosamine residues. On the other hand, silica did not stimulate superoxide anion production. The effect of silica on agonist stimulation of this pathway was examined using two stimulants of superoxide anion production, N-formyl-nle-leu-phe (FNLP, which stimulates through phospholipase C) and phorbol-12,13-dibutyrate (which directly activates protein kinase C).
- Research Organization:
- Texas Univ., Houston, TX (USA). School of Public Health
- OSTI ID:
- 6808413
- Resource Relation:
- Other Information: Thesis (Ph. D.)
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
ASBESTOS
BIOLOGICAL EFFECTS
CALCIUM COMPOUNDS
MEMBRANE TRANSPORT
PHOSPHOLIPIDS
METABOLISM
SILICA
SUPEROXIDE RADICALS
BIOSYNTHESIS
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL PATHWAYS
ENZYME ACTIVITY
GUINEA PIGS
LECTINS
LIPASES
MACROPHAGES
RECEPTORS
TOXINS
ALKALINE EARTH METAL COMPOUNDS
ANIMAL CELLS
ANIMALS
ANTIGENS
CARBOXYLESTERASES
CHALCOGENIDES
CONNECTIVE TISSUE CELLS
ENZYMES
ESTERASES
ESTERS
HYDROLASES
KINETICS
LIPIDS
MAMMALS
MATERIALS
MEMBRANE PROTEINS
MINERALS
ORGANIC COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
OXIDE MINERALS
OXIDES
OXYGEN COMPOUNDS
PHAGOCYTES
PROTEINS
RADICALS
REACTION KINETICS
RODENTS
SILICON COMPOUNDS
SILICON OXIDES
SOMATIC CELLS
SYNTHESIS
TOXIC MATERIALS
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology