Cigarette smoke-induced airway hyperresponsiveness is not dependent on elevated immunoglobulin and eosinophilic inflammation in a mouse model of allergic airway disease

Am J Respir Crit Care Med. 2002 May 15;165(10):1410-8. doi: 10.1164/rccm.2106029.


Epidemiologic studies suggest that children raised in homes of cigarette smokers have a higher incidence of asthma than children who are raised in homes of nonsmokers. We sought to develop an experimental model to understand the mechanisms involved. Female BALB/c mice were paired with male DO11.10 ovalbumin (OVA)-T cell receptor hemizygous (+/-) mice such that the offspring were either transgene positive (+/-) or negative (-/-). Mice were exposed to either air or mainstream cigarette smoke (100 mg/m(3) total particulate matter, 6 hours/day, 7 days/week) during pregnancy. Immediately after birth, newborn mice were exposed for 4 weeks to either air or sidestream cigarette smoke (SS; 5 mg/m(3) total particulate matter, 6 hours/day, 5 days/week) and then exposed for the following 6 weeks to either air, SS, OVA (5 mg/m(3), 6 hours/day, 5 days/week) or a combination of OVA-SS. DO11.10 +/- offspring exposed to OVA had increased airway hyperresponsiveness (AHR) to methacholine challenge, total IgE, OVA-specific IgE and IgG(1), lymphocytes, and neutrophils in bronchoalveolar lavage and perivascular and peribronchiolar inflammation. Exposure to SS alone caused a significant increase in AHR in both +/- and -/- mice. Transgene -/- mice did not exhibit AHR after OVA exposure unless it was delivered in combination with SS. When compared with OVA-only exposure, OVA-SS exposure decreased total IgE, OVA-specific IgE, and IgG(1) amounts in +/- mice. These results indicate that exposure to SS after birth enhanced AHR in offspring that are both predisposed (+/-) and nonpredisposed (-/-) to develop an allergic response to OVA, but this AHR was not associated with elevated lung eosinophilia or OVA-specific Ig amounts.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Administration, Inhalation
  • Analysis of Variance
  • Animals
  • Bronchoalveolar Lavage Fluid / immunology
  • Disease Models, Animal
  • Eosinophilia / immunology*
  • Female
  • Immunoglobulin E / analysis
  • Immunoglobulin E / immunology
  • Immunoglobulin G / analysis
  • Immunoglobulin G / immunology
  • Immunoglobulins / analysis
  • Immunoglobulins / immunology*
  • Immunohistochemistry
  • Lung / pathology
  • Mice
  • Mice, Inbred BALB C
  • Ovalbumin
  • Photomicrography
  • Pregnancy
  • Pregnancy, Animal
  • Probability
  • Respiratory Hypersensitivity / immunology*
  • Respiratory Hypersensitivity / pathology
  • Smoke / adverse effects*


  • Immunoglobulin G
  • Immunoglobulins
  • Smoke
  • Immunoglobulin E
  • Ovalbumin