Cigarette smoke-induced airway hyperresponsiveness is not dependent on elevated immunoglobulin and eosinophilic inflammation in a mouse model of allergic airway disease.
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.
Barrett
Edward G
EG
Respiratory Immunology Program, Lovelace Respiratory Research Institute, Albequerque, New Mexico 87108, USA. tbarrett@lrri.org
Wilder
Julie A
JA
March
Thomas H
TH
Espindola
Teresa
T
Bice
David E
DE
D000280:Administration, Inhalation; D000704:Analysis of Variance; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D004195:Disease Models, Animal; D004802:Eosinophilia / Q000276:immunology*; D005260:Female; D007073:Immunoglobulin E / Q000032:analysis / Q000276:immunology; D007074:Immunoglobulin G / Q000032:analysis / Q000276:immunology; D007136:Immunoglobulins / Q000032:analysis / Q000276:immunology*; D007150:Immunohistochemistry; D008168:Lung / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin; D010784:Photomicrography; D011247:Pregnancy; D011270:Pregnancy, Animal; D011336:Probability; D012130:Respiratory Hypersensitivity / Q000276:immunology* / Q000473:pathology; D012906:Smoke / Q000009:adverse effects*
D007074:Immunoglobulin G; D007136:Immunoglobulins; D012906:Smoke; D007073:Immunoglobulin E; D010047:Ovalbumin