Oxidant stress modulates murine allergic airway responses.
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 F2-isoprostanes. F2-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-F2t-IsoP (8-iso-PGF2alpha) or to isoketal protein adducts was found in epithelial cells 24 h after the first aerosol challenge and at 5 days in macrophages. 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 F2-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.
Talati
Megha
M
Department of Medicine, T 1217 MCN, Vanderbilt University, Nashville, TN 37232, USA.
Meyrick
Barbara
B
Peebles
R Stokes
RS
Davies
Sean S
SS
Dworski
Ryszard
R
Mernaugh
Ray
R
Mitchell
Daphne
D
Boothby
Mark
M
Roberts
L Jackson
LJ
Sheller
James R
JR
D000818:Animals; D001249:Asthma / Q000276:immunology / Q000503:physiopathology*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D028441:F2-Isoprostanes / Q000502:physiology*; D005260:Female; D015227:Lipid Peroxidation / Q000187:drug effects; D008168:Lung / Q000276:immunology / Q000502:physiology; D016676:Macrophages, Alveolar / Q000737:chemistry; D016210:Methacholine Chloride; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology; D018384:Oxidative Stress; D013047:Specific Pathogen-Free Organisms; D021241:Spectrometry, Mass, Electrospray Ionization; D014810:Vitamin E / Q000008:administration & dosage / Q000097:blood; D014811:Vitamin E Deficiency / Q000503:physiopathology
D016207:Cytokines; D028441:F2-Isoprostanes; D016210:Methacholine Chloride; D014810:Vitamin E; D010047:Ovalbumin