Cell-specific oxidative stress and cytotoxicity after wildfire coarse particulate matter instillation into mouse lung

Keisha M. Williams, Lisa M. Franzi, Jerold A Last

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Our previous work has shown that coarse particulate matter (PM10-2.5) from wildfire smoke is more toxic to lung macrophages on an equal dose (by mass) basis than coarse PM isolated from normal ambient air, as evidenced by decreased numbers of macrophages in lung lavage fluid 6 and 24hours after PM instillation into mouse lungs in vivo and by cytotoxicity to a macrophage cell line observed directly in vitro. We hypothesized that pulmonary macrophages from mice instilled with wildfire coarse PM would undergo more cytotoxicity than macrophages from controls, and that there would be an increase in oxidative stress in their lungs. Cytotoxicity was quantified as decreased viable macrophages and increased percentages of dead macrophages in the bronchoalveolar lavage fluid (BALF) of mice instilled with wildfire coarse PM. At 1hour after PM instillation, we observed both decreased numbers of viable macrophages and increased dead macrophage percentages as compared to controls. An increase in free isoprostanes, an indicator of oxidative stress, from control values of 28.1±3.2pg/mL to 83.9±12.2pg/mL was observed a half-hour after PM instillation. By 1hour after PM instillation, isoprostane values had returned to 30.4±7.6pg/mL, not significantly different from control concentrations. Lung sections from mice instilled with wildfire coarse PM showed rapid Clara cell responses, with decreased intracellular staining for the Clara cell secretory protein CCSP 1hour after wildfire PM instillation. In conclusion, very rapid cytotoxicity occurs in pulmonary macrophages and oxidative stress responses are seen 0.5-1hour after wildfire coarse PM instillation. These results define early cellular and biochemical events occurring in vivo and support the hypothesis that oxidative stress-mediated macrophage toxicity plays a key role in the initial response of the mouse lung to wildfire PM exposure.

Original languageEnglish (US)
Pages (from-to)48-55
Number of pages8
JournalToxicology and Applied Pharmacology
Volume266
Issue number1
DOIs
StatePublished - Jan 1 2013

Fingerprint

Oxidative stress
Particulate Matter
Macrophages
Cytotoxicity
Oxidative Stress
Lung
Isoprostanes
Bronchoalveolar Lavage Fluid
Alveolar Macrophages
Uteroglobin
Fluids
Poisons
Smoke
Toxicity
Air
Cells
Staining and Labeling
Cell Line

Keywords

  • CCSP
  • Clara cells
  • Isoprostanes
  • Macrophage
  • PM
  • TNF-α

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

Cell-specific oxidative stress and cytotoxicity after wildfire coarse particulate matter instillation into mouse lung. / Williams, Keisha M.; Franzi, Lisa M.; Last, Jerold A.

In: Toxicology and Applied Pharmacology, Vol. 266, No. 1, 01.01.2013, p. 48-55.

Research output: Contribution to journalArticle

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