Journal
FREE RADICAL BIOLOGY AND MEDICINE
Volume 40, Issue 7, Pages 1210-1219Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2005.11.012
Keywords
asthma; isoprostanes; free radicals; macrophages; epithelial cells; eosinophils; chitinase
Funding
- NHLBI NIH HHS [HL61752, HL 069949] Funding Source: Medline
- NIAID NIH HHS [AI 054660] Funding Source: Medline
- NIGMS NIH HHS [GM42056] Funding Source: Medline
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The allergic inflammation occurring in asthma is believed to be accompanied by the production of free radicals. To investigate the role of free radicals and the cells affected we turned to a murine model of allergic inflammation produced by sensitization to ovalbumin with subsequent aerosol challenge. We examined oxidant stress by measuring and localizing the sensitive and specific marker of lipid peroxidation, the F-2-isoprostanes. F-2-isoprostanes in whole lung increased from 0.30 +/- 0.08 ng/lung at baseline to a peak of 0.061 +/- 0,09 ng/lung on the ninth day of daily aerosol allergen challenge. Increased immunoreactivity to 15-F-2t-ISOP (8-iso-PGF(2 alpha)) or to isoketal protein adducts was found in epithelial cells 24 It after the first aerosol challenge and at 5 days in macropbages. Collagen surrounding airways and blood vessels, and airway and vascular smooth muscle, also exhibited increased immunoreactivity after ovalbumin challenge. Dietary vitamin E restriction in conjunction with allergic inflammation led to increased whole lung F2-isoprostanes while supplemental vitamin E suppressed their formation. Similar changes in immunoreactivity to F-2-isoprostanes were seen. Airway responsiveness to methacholine was also increased by vitamin E depletion and decreased slightly by supplementation with the antioxidant. Our findings indicate that allergic airway inflammation in mice is associated with an increase in oxidant stress, which is most striking in airway epithelial cells and macrophages. Oxidant stress plays a role in the production of airway responsiveness. (c) 2005 Elsevier Inc. All rights reserved.
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