Auten, RL; Potts, EN; Mason, SN; Fischer, B; Huang, Y; Foster, WM
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: Determine if maternal pulmonary exposure to traffic-related particles during pregnancy augments ozone-induced airway hyperresponsiveness in offspring. Methods and Main Results: C57BL6 time-mated mice were given NIST SRM#1648 (PM) 0.48 mg, saline vehicle, or no treatment by tracheal insufflation twice weekly for three weeks. PM exposure augmented maternal lung inflammation and placental TNF, KC, and IL-6 (measured at gestation day 18). After parturition, dams and litters were exposed to air or ozone 1 ppm 3 hours/day, every other day, thrice weekly for four weeks. Respiratory system resistance in pups was measured at baseline and after administration of nebulized methacholine. Ozone increased airway hyperresponsiveness, but the increase was greatest in pups born to PM-treated dams. Whole lung TNF, IL-1, KC, IL-6, and MCP-1 were all 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 -actin histochemistry, were unaffected by pre- or post-natal treatment. Conclusion: 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.
