Priming of allergic immune responses by repeated ozone exposure in mice.
The effects of repeated ozone exposures on the development of immune responses toward ovalbumin (OVA) were investigated in BALB/c and C57BL/6 mice. Ozone exposures (180 to 500 microg/m(3); 4 h, three times/wk for 4 wk) were combined with a protocol of OVA-aerosol exposure (1% OVA). Immediate cutaneous hypersensitivity (ICHS) reactions and antibody titers were assessed in parallel to cytokine levels of bronchoalveolar lavage fluids. In BALB/c mice, ozone triggered a T-helper (Th)2-like response indicated by dose-dependent increases in total serum immunoglobulin (Ig) E (from 133 to 821 ng/ml), interleukin (IL)-4 (from 60 to 208 pg/ml), and IL-5 levels (from 43 to 356 pg/ml), and by the recruitment of eosinophils and lymphocytes into the airways. Ozone exposure (500 microg/m(3)) in parallel to OVA-aerosol exposure increased anti-OVA IgG(1) antibody titers by 80%, leukotrienes (C(4)/D(4)/E(4)) by 60%, and airway responsiveness (11.3 versus 7.2 mg/ml methacholine), and doubled the frequency of positive ICHS reactions. In C57BL/6 mice, only the combination of OVA and ozone exposure induced positive ICHS reactions, doubled anti-OVA IgG(1), and suppressed anti-OVA IgG(2a) (-64%) antibody titers. Ozone, therefore, shifted the immune responses to OVA toward a Th2-like pattern in both "IgE-high responder" (BALB/c) and "IgE-low responder" (C57BL/6) mice.
Institute of Laboratory Medicine and Pathobiochemistry, Charité Campus Virchow Clinic, Berlin, Germany.
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Neuhaus-Steinmetz
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Uffhausen
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Herz
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Renz
D000280:Administration, Inhalation; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002452:Cell Count / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006969:Hypersensitivity, Immediate / Q000276:immunology*; D007073:Immunoglobulin E / Q000097:blood / Q000187:drug effects; D007074:Immunoglobulin G / Q000097:blood / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology / Q000494:pharmacology; D010083:Oxidants, Photochemical / Q000494:pharmacology*; D010126:Ozone / Q000494:pharmacology*; D018418:Th2 Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology
D007074:Immunoglobulin G; D010083:Oxidants, Photochemical; D007073:Immunoglobulin E; D010126:Ozone; D010047:Ovalbumin