Mice that overexpress Cu/Zn superoxide dismutase are resistant to allergen-induced changes in airway control.
Within the respiratory epithelium of asthmatic patients, copper/zinc-containing superoxide dismutase (Cu/Zn SOD) is decreased. To address the hypothesis that lung Cu/Zn SOD protects against allergen-induced injury, wild-type and transgenic mice that overexpress human Cu/Zn SOD were either passively sensitized to ovalbumin (OVA) or actively sensitized by repeated airway exposure to OVA. Controls included nonsensitized wild-type and transgenic mice given intravenous saline or airway exposure to saline. After aerosol challenge to saline or OVA, segments of tracheal smooth muscle were obtained for in vitro analysis of neural control. In response to electrical field stimulation, wild-type sensitized mice challenged with OVA had significant increases in cholinergic reactivity. Conversely, sensitized transgenic mice challenged with OVA were resistant to changes in neural control. Stimulation of tracheal smooth muscle to elicit acetylcholine release showed that passively sensitized wild-type but not transgenic mice released more acetylcholine after OVA challenge. Function of the M(2) muscarinic autoreceptor was preserved in transgenic mice. These results demonstrate that murine airways with elevated Cu/Zn SOD were resistant to allergen-induced changes in neural control.
Divisions of Pediatric Pulmonary Medicine and Basic Sciences, Department of Pediatrics, National Jewish Medical and Research Center, Denver, Colorado 80206, USA.
G L
GL
Larsen
C W
CW
White
K
K
Takeda
J E
JE
Loader
D D
DD
Nguyen
A
A
Joetham
Y
Y
Groner
E W
EW
Gelfand
D000109:Acetylcholine / Q000378:metabolism / Q000494:pharmacology; D000280:Administration, Inhalation; D000485:Allergens / Q000008:administration & dosage / Q000276:immunology*; D000818:Animals; D016084:Bronchoconstriction / Q000187:drug effects / Q000276:immunology / Q000502:physiology; D002851:Chromatography, High Pressure Liquid; D004558:Electric Stimulation; D004804:Eosinophils / Q000166:cytology; D006801:Humans; D007114:Immunization; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008168:Lung / Q000166:cytology / Q000276:immunology; D016210:Methacholine Chloride / Q000494:pharmacology; D051379:Mice; D008822:Mice, Transgenic; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D043585:Receptor, Muscarinic M2; D011976:Receptors, Muscarinic / Q000378:metabolism; D013482:Superoxide Dismutase / Q000096:biosynthesis*; D014132:Trachea / Q000201:enzymology* / Q000276:immunology* / Q000294:innervation
D000485:Allergens; D043585:Receptor, Muscarinic M2; D011976:Receptors, Muscarinic; D016210:Methacholine Chloride; D010047:Ovalbumin; D013482:Superoxide Dismutase; D000109:Acetylcholine