Maternal exposure to particulate matter increases postnatal ozone-induced airway hyperreactivity in juvenile mice.
BACKGROUND
Epidemiologic studies implicate air pollutant exposure during pregnancy as a risk factor for wheezing in offspring. Ozone exposure is linked to exacerbations of wheezing in children.


OBJECTIVE
To determine if maternal pulmonary exposure to traffic-related particles during pregnancy augments ozone-induced airway hyperresponsiveness in offspring.


METHODS
C57BL6 time-mated mice were given NIST SRM#1648 (particulate matter [PM]) 0.48 mg, saline vehicle, or no treatment by tracheal insufflation twice weekly for 3 weeks. PM exposure augmented maternal lung inflammation and placental TNF-alpha, Keratinocyte-derived cytokine (KC), and IL-6 (measured at gestation Day 18). After parturition, dams and litters were exposed to air or ozone 1 ppm 3 h/d, every other day, thrice weekly for 4 weeks. Respiratory system resistance in pups was measured at baseline and after administration of nebulized methacholine.


RESULTS
Ozone increased airway hyperresponsiveness, but the increase was greatest in pups born to PM-treated dams. Whole-lung TNF-alpha, IL-1beta, KC, IL-6, and MCP-1 were increased in ozone-treated pups, with the greatest increase in pups born to dams given PM. Airway epithelial mucous metaplasia estimated by periodic acid-Schiff Alcian blue staining was increased in ozone-exposed pups born to PM-treated dams. Alveolar development, determined by morphometry, and airway smooth muscle bulk, estimated using alpha-actin histochemistry, were unaffected by prenatal or postnatal treatment.


CONCLUSIONS
Maternal pulmonary exposure to PM during pregnancy augments placental cytokine expression and postnatal ozone-induced pulmonary inflammatory cytokine responses and ozone-induced airway hyperresponsiveness without altering airway structure.
Auten
Richard L
RL
Neonatal Medicine, Department of Pediatrics, Duke University, Durham, North Carolina, USA. auten@duke.edu
Potts
Erin N
EN
Mason
S Nicholas
SN
Fischer
Bernard
B
Huang
Yuhchin
Y
Foster
W Michael
WM
D000393:Air Pollutants / Q000633:toxicity; D000397:Air Pollution; D000704:Analysis of Variance; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000139:chemically induced* / Q000503:physiopathology; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid; D004195:Disease Models, Animal; D005260:Female; D007249:Inflammation / Q000139:chemically induced / Q000503:physiopathology; D019570:Inhalation Exposure; D008168:Lung / Q000503:physiopathology; D018811:Maternal Exposure; D008431:Maternal-Fetal Exchange; D051379:Mice; D008810:Mice, Inbred C57BL; D010083:Oxidants, Photochemical / Q000633:toxicity*; D010126:Ozone / Q000633:toxicity*; D052638:Particulate Matter / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced*; D012129:Respiratory Function Tests
D000393:Air Pollutants; D010083:Oxidants, Photochemical; D052638:Particulate Matter; D010126:Ozone