Quantifying the magnitude of the oxygen artefact inherent in culturing airway cells under atmospheric oxygen versus physiological levels

TY - JOUR

T1 - Quantifying the magnitude of the oxygen artefact inherent in culturing airway cells under atmospheric oxygen versus physiological levels

AU - Kumar, Abhinav

AU - Dailey, Lea Ann

AU - Swedrowska, Magda

AU - Siow, Richard

AU - Mann, Giovanni E.

AU - Vizcay-Barrena, Gema

AU - Arno, Matthew

AU - Mudway, Ian S.

AU - Forbes, Ben

PY - 2016/1/23

Y1 - 2016/1/23

N2 - To date, in vitro studies assessing the pulmonary toxicity of inhaled particles have provided poor correlation with in vivo results. We explored whether this discrepancy reflected cellular adaptations in pulmonary cells cultured under atmospheric oxygen concentrations (21%) compared with in vivo alveolar concentrations (100 mm Hg, ∼13%) and whether this blunted cellular responses to nanoparticle challenge. At 21% oxygen, A549 cells had augmented intracellular glutathione concentrations, with evidence of increased tolerance to CuO nanoparticles, with reduced reactive oxygen species production, blunted transcriptional responses and delayed cell death, compared to cells cultured at 13% oxygen. These data support the contention that standard cell culture conditions pre-adapt cells to oxidative insults and emphasize the necessity of ensuring normoxic conditions in model systems to improve their predictive value.

AB - To date, in vitro studies assessing the pulmonary toxicity of inhaled particles have provided poor correlation with in vivo results. We explored whether this discrepancy reflected cellular adaptations in pulmonary cells cultured under atmospheric oxygen concentrations (21%) compared with in vivo alveolar concentrations (100 mm Hg, ∼13%) and whether this blunted cellular responses to nanoparticle challenge. At 21% oxygen, A549 cells had augmented intracellular glutathione concentrations, with evidence of increased tolerance to CuO nanoparticles, with reduced reactive oxygen species production, blunted transcriptional responses and delayed cell death, compared to cells cultured at 13% oxygen. These data support the contention that standard cell culture conditions pre-adapt cells to oxidative insults and emphasize the necessity of ensuring normoxic conditions in model systems to improve their predictive value.

KW - dose

KW - lung

KW - nanoparticle

KW - normoxia

KW - oxidative stress

KW - oxygen

UR - http://www.scopus.com/inward/record.url?scp=84957310347&partnerID=8YFLogxK

U2 - 10.1002/1873-3468.12026

DO - 10.1002/1873-3468.12026

M3 - Article

AN - SCOPUS:84957310347

SN - 0014-5793

VL - 590

SP - 258

EP - 269

JO - FEBS Letters

JF - FEBS Letters

IS - 2

ER -