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Sex Modifies Acute Ozone-Mediated Airway Physiologic Responses.

Publication ,  Journal Article
Birukova, A; Cyphert-Daly, J; Cumming, RI; Yu, Y-R; Gowdy, KM; Que, LG; Tighe, RM
Published in: Toxicol Sci
June 1, 2019

Sex differences clearly exist in incidence, susceptibility, and severity of airway disease and in pulmonary responses to air pollutants such as ozone (O3). Prior rodent O3 exposure studies demonstrate sex-related differences in the expression of lung inflammatory mediators and signaling. However, whether or not sex modifies O3-induced airway physiologic responses remains less explored. To address this, we exposed 8- to 10-week-old male and female C57BL/6 mice to either 1 or 2 ppm O3 or filtered air (FA) for 3 h. At 12, 24, 48, and 72 h following exposure, we assessed airway hyperresponsiveness to methacholine (MCh), bronchoalveolar lavage fluid cellularity, cytokines and total protein/albumin, serum progesterone, and whole lung immune cells by flow cytometry. Male mice generated consistent airway hyperresponsiveness to MCh at all time points following exposure. Alternatively, females had less consistent airway physiologic responses to MCh, which were more variable between individual experiments and did not correlate with serum progesterone levels. Bronchoalveolar lavage fluid total cells peaked at 12 h and were persistently elevated through 72 h. At 48 h, bronchoalveolar lavage cells were greater in females versus males. Bronchoalveolar lavage fluid cytokines and total protein/albumin increased following O3 exposure without sex differences. Flow cytometry of whole lung tissue identified dynamic O3-induced immune cell changes also independent of sex. Our results indicate sex differences in acute O3-induced airway physiology responses and airspace influx without significant difference in other injury and inflammation measures. This study highlights the importance of considering sex as a biological variable in acute O3-induced airway physiology responses.

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Published In

Toxicol Sci

DOI

EISSN

1096-0929

Publication Date

June 1, 2019

Volume

169

Issue

2

Start / End Page

499 / 510

Location

United States

Related Subject Headings

  • Toxicology
  • Sex Characteristics
  • Respiratory Hypersensitivity
  • Progesterone
  • Ozone
  • Mice, Inbred C57BL
  • Mice
  • Methacholine Chloride
  • Male
  • Immunophenotyping
 

Citation

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Chicago
ICMJE
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Birukova, A., Cyphert-Daly, J., Cumming, R. I., Yu, Y.-R., Gowdy, K. M., Que, L. G., & Tighe, R. M. (2019). Sex Modifies Acute Ozone-Mediated Airway Physiologic Responses. Toxicol Sci. United States. https://doi.org/10.1093/toxsci/kfz056
Birukova, Anastasiya, Jaime Cyphert-Daly, Robert Ian Cumming, Yen-Rei Yu, Kymberly M. Gowdy, Loretta G. Que, and Robert M. Tighe. “Sex Modifies Acute Ozone-Mediated Airway Physiologic Responses.Toxicol Sci, June 1, 2019. https://doi.org/10.1093/toxsci/kfz056.
Birukova A, Cyphert-Daly J, Cumming RI, Yu Y-R, Gowdy KM, Que LG, et al. Sex Modifies Acute Ozone-Mediated Airway Physiologic Responses. Vol. 169, Toxicol Sci. 2019. p. 499–510.
Birukova, Anastasiya, et al. “Sex Modifies Acute Ozone-Mediated Airway Physiologic Responses.Toxicol Sci, vol. 169, no. 2, 1 June 2019, pp. 499–510. Pubmed, doi:10.1093/toxsci/kfz056.
Birukova A, Cyphert-Daly J, Cumming RI, Yu Y-R, Gowdy KM, Que LG, Tighe RM. Sex Modifies Acute Ozone-Mediated Airway Physiologic Responses. Toxicol Sci. 2019. p. 499–510.
Journal cover image

Published In

Toxicol Sci

DOI

EISSN

1096-0929

Publication Date

June 1, 2019

Volume

169

Issue

2

Start / End Page

499 / 510

Location

United States

Related Subject Headings

  • Toxicology
  • Sex Characteristics
  • Respiratory Hypersensitivity
  • Progesterone
  • Ozone
  • Mice, Inbred C57BL
  • Mice
  • Methacholine Chloride
  • Male
  • Immunophenotyping