Pulmonary exposure to particles during pregnancy causes increased neonatal asthma susceptibility

Alexey V. Fedulov*, Adriana Leme, Zhiping Yang, Morten Dahl, Robert Lim, Thomas J. Mariani, Lester Kobzik

*Corresponding author af dette arbejde

    Publikation: Bidrag til tidsskriftArtikelForskningpeer review

    Abstract

    Maternal immune responses can promote allergy development in offspring, as shown in a model of increased susceptibility to asthma in babies of ovalbumin (OVA)-sensitized and -challenged mother mice. We investigated whether inflammatory responses to air pollution particles (diesel exhaust particles, DEP) or control "inert" titanium dioxide (TiO2) particles are enhanced during pregnancy and whether exposure to particles can cause increased neonatal susceptibility to asthma. Pregnant BALB/c mice (or nonpregnant controls) received particle suspensions intranasally at Day 14 of pregnancy. Lung inflammatory responses were evaluated 48 hours after exposure. Offspring of particle- or buffer-treated mothers were sensitized and aerosolized with OVA, followed by assays of airway hyperresponsiveness (AHR) and allergic inflammation (AI). Non-pregnant females had the expected minimal response to "inert" TiO2. In contrast, pregnant mice showed robust and persistent acute inflammation after both TiO2 and DEP. Genomic profiling identified genes differentially expressed in pregnant lungs exposed to TiO2. Neonates of mothers exposed to TiO2 (and DEP, but not PBS) developed AHR and AI, indicating that pregnancy exposure to both "inert" TiO2 and DEP caused increased asthma susceptibility in offspring. We conclude that (1) pregnancy enhances lung inflammatory responses to otherwise relatively innocuous inert particles; and (2) exposures of nonallergic pregnant females to inert or toxic environmental air particles can cause increased allergic susceptibility in offspring.

    OriginalsprogEngelsk
    Sider (fra-til)57-67
    Antal sider11
    TidsskriftAmerican Journal of Respiratory Cell and Molecular Biology
    Vol/bind38
    Udgave nummer1
    DOI
    StatusUdgivet - 1 jan. 2008

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