title: Maternal exposure to combustion generated PM inhibits pulmonary Th1 maturation and concomitantly enhances postnatal asthma development in offspring.
abstract: BACKGROUND
  Epidemiological studies suggest that maternal exposure to environmental hazards, such as particulate matter, is associated with increased incidence of asthma in childhood. We hypothesized that maternal exposure to combustion derived ultrafine particles containing persistent free radicals (MCP230) disrupts the development of the infant immune system and results in aberrant immune responses to allergens and enhances asthma severity.
  
  
  METHODS
  Pregnant C57/BL6 mice received MCP230 or saline by oropharyngeal aspiration on gestational days 10 and 17. Three days after the second administration, blood was collected from MCP230 or saline treated dams and 8-isoprostanes in the serum were measured to assess maternal oxidative stress. Pulmonary T cell populations were assayed in the infant mice at six days, three and six weeks of postnatal age. When the infant mice matured to adults (i.e. six weeks of age), an asthma model was established with ovalbumin (OVA). Airway inflammation, mucus production and airway hyperresponsiveness were then examined.
  
  
  RESULTS
  Maternal exposure to MCP230 induced systemic oxidative stress. The development of pulmonary T helper (Th1/Th2/Th17) and T regulatory (Treg) cells were inhibited in the infant offspring from MCP230-exposed dams. As the offspring matured, the development of Th2 and Treg cells recovered and eventually became equivalent to that of offspring from non-exposed dams. However, Th1 and Th17 cells remained attenuated through 6 weeks of age. Following OVA sensitization and challenge, mice from MCP230-exposed dams exhibited greater airway hyperresponsiveness, eosinophilia and pulmonary Th2 responses compared to offspring from non-exposed dams.
  
  
  CONCLUSIONS
  Our data suggest that maternal exposure to MCP230 enhances postnatal asthma development in mice, which might be related to the inhibition of pulmonary Th1 maturation and systemic oxidative stress in the dams.
authors.forename: Pingli
authors.initials: P
authors.lastname: Wang
authors.forename: Dahui
authors.initials: D
authors.lastname: You
authors.forename: Jordy
authors.initials: J
authors.lastname: Saravia
authors.forename: Huahao
authors.initials: H
authors.lastname: Shen
authors.forename: Stephania A
authors.initials: SA
authors.lastname: Cormier
mesh_terms: D000367:Age Factors; D000818:Animals; D001249:Asthma / Q000097:blood / Q000139:chemically induced* / Q000175:diagnosis / Q000276:immunology; D016535:Bronchial Hyperreactivity / Q000097:blood / Q000139:chemically induced* / Q000175:diagnosis / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D015237:Dinoprost / Q000031:analogs & derivatives / Q000097:blood; D005260:Female; D005865:Gestational Age; D018836:Inflammation Mediators / Q000378:metabolism; D019570:Inhalation Exposure / Q000009:adverse effects*; D008168:Lung / Q000187:drug effects* / Q000196:embryology / Q000276:immunology / Q000378:metabolism; D018811:Maternal Exposure / Q000009:adverse effects*; D008810:Mice, Inbred C57BL; D010047:Ovalbumin; D018384:Oxidative Stress / Q000187:drug effects; D052638:Particulate Matter / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011657:Pulmonary Eosinophilia / Q000139:chemically induced / Q000276:immunology; D012720:Severity of Illness Index; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology; D018417:Th1 Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D058504:Th17 Cells / Q000187:drug effects / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D052638:Particulate Matter; C075750:8-epi-prostaglandin F2alpha; D010047:Ovalbumin; D015237:Dinoprost