Maternal exposure to particulate matter increases postnatal ozone-induced airway hyperreactivity in juvenile mice.
RATIONALE: 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. OBJECTIVES: 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. MEASUREMENTS AND MAIN 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, RL; Potts, EN; Mason, SN; Fischer, B; Huang, Y; Foster, WM
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