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Maternal Exposure to Particulate Matter Increases Postnatal Ozone-induced Airway Hyperreactivity in Juvenile Mice

¹ Neonatal Medicine, Department of Pediatrics; ² Pulmonary and Critical Care Medicine, Department of Medicine; and ³ Pulmonary Medicine, Department of Pediatrics, Duke University, Durham, North Carolina

Correspondence and requests for reprints should be addressed to R. L. Auten, M.D., DUMC Box 3373, Duke University Medical Center, Durham, NC 27710. E-mail: auten{at}duke.edu

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-, 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-, IL-1β, 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 -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.

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Maternal pulmonary exposure to air pollutants augments antigen-induced airway hyperresponsiveness in juvenile mice. Interaction with ozone-induced hyperresponsivity has not been tested. What This Study Adds to the Field Maternal exposure of mice to particulate matter augments placental inflammatory cytokine responses and ozone-induced lung inflammation and airway hyperreactivity in offspring.