Sex Modifies Acute Ozone-Mediated Airway Physiologic Responses
Open Access
- 2 March 2019
- journal article
- research article
- Published by Oxford University Press (OUP) in Toxicological Sciences
- Vol. 169 (2), 499-510
- https://doi.org/10.1093/toxsci/kfz056
Abstract
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.Keywords
Funding Information
- National Institutes of Health (K08 HL105537, R01 ES027574)
- United States Environmental Protection Agency (R-82811201)
This publication has 61 references indexed in Scilit:
- Health Benefits from Large-Scale Ozone Reduction in the United StatesEnvironmental Health Perspectives, 2012
- Sex Differences and Sex Steroids in Lung Health and DiseaseEndocrine Reviews, 2012
- Ozone Inhalation Promotes CX3CR1-Dependent Maturation of Resident Lung Macrophages That Limit Oxidative Stress and InflammationThe Journal of Immunology, 2011
- Pulmonary function, bronchial reactivity, and epithelial permeability are response phenotypes to ozone and develop differentially in healthy humansJournal of Applied Physiology, 2011
- Short-term Associations between Ambient Air Pollutants and Pediatric Asthma Emergency Department VisitsAmerican Journal of Respiratory and Critical Care Medicine, 2010
- Hyaluronan Mediates Ozone-induced Airway Hyperresponsiveness in MiceOnline Journal of Public Health Informatics, 2009
- Male sex hormones promote vagally mediated reflex airway responsiveness to cholinergic stimulationAmerican Journal of Physiology-Lung Cellular and Molecular Physiology, 2007
- Spontaneous Airway Hyperresponsiveness in Estrogen Receptor-α–deficient MiceAmerican Journal of Respiratory and Critical Care Medicine, 2007
- Acute Pulmonary Function Response to Ozone in Young Adults As a Function of Body Mass IndexInhalation Toxicology, 2007
- The relationship of sex to asthma prevalence, health care utilization, and medications in a large managed care organizationAnnals of Allergy, Asthma & Immunology, 2003