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Asbestos effects on superoxide production. An in vitro study of hamster alveolar macrophages
Abstract:
Inhaled asbestos induces accumulation of alveolar macrophages (AM) and polymorphonuclear leukocytes (PMN) in lung. Asbestos-enhanced production of superoxide anion (O2-) by AM and/or PMN may be involved in the pathogenesis of asbestos-induced fibrosis, either through direct effects on collagen synthesis or via mediation of tissue injury and repair. In in vivo experiments, bronchoalveolar lavage (BAL) 3 to 8 weeks following intratracheal asbestos injections showed increases in both PMN and AM, with AM representing 78 to 82% of cells recovered. Inhalation models, generally regarded as more analagous to human exposures, have confirmed AM as the predominant component of the cellular response to inhaled asbestos. In this study, the in vitro effects of asbestos fiber on O2- production by AM have been determined in cell populations derived from the Syrian golden hamster. AM for in vitro study were obtained by BAL. O2- production was monitored as superoxide dismutase (SOD) - inhibitable cytochrome c reduction. Significant rises in O2- release by AM were noted in the presence of 0.4 mg/ml crocidolite (2.53 +/- 0.33 nmole cytochrome c reduced/10(6) cells/30 min, 37 degrees C; controls 1.13 +/- 0.18 nmole; P less than 0.02). Chrysotile induced levels of O2- release in AM which were similar to those evoked by crocidolite.
Insights
Inhaled asbestos significantly increases superoxide anion (O2-) release by alveolar macrophages (AM). This asbestos-induced O2- production by AM may contribute to lung fibrosis development.
Area of Science:
- Pulmonary toxicology
- Cellular immunology
Background:
- Inhaled asbestos triggers lung inflammation, involving alveolar macrophages (AM) and polymorphonuclear leukocytes (PMN).
- Asbestos-mediated superoxide anion (O2-) production by these cells is a potential factor in asbestos-induced lung fibrosis.
- Inhalation studies confirm AM as the primary cellular responders to inhaled asbestos.
Purpose of the Study:
- To investigate the in vitro effects of asbestos fibers on O2- production by AM.
- To quantify O2- release from AM exposed to specific asbestos types.
Main Methods:
- Alveolar macrophages (AM) were obtained from Syrian golden hamsters via bronchoalveolar lavage (BAL).
- In vitro asbestos exposure (crocidolite and chrysotile) was performed on isolated AM.
- Superoxide anion (O2-) production was measured by monitoring superoxide dismutase (SOD)-inhibitable cytochrome c reduction.
Main Results:
- Significant increases in O2- release were observed in AM exposed to 0.4 mg/ml crocidolite compared to controls (P < 0.02).
- Chrysotile asbestos exposure induced similar levels of O2- release from AM as crocidolite.
Conclusions:
- Asbestos fibers directly stimulate AM to release increased amounts of superoxide anion (O2-).
- This asbestos-induced O2- production by AM is a key cellular response and may play a role in the pathogenesis of asbestos-related lung diseases like fibrosis.

