Acute inhibition of nitric oxide exacerbates airway hyperresponsiveness, eosinophilia and C-C chemokine generation in a murine model of fungal asthma.
OBJECTIVE
This study examined the role of nitric oxide in changes in airway physiology and inflammation in a murine model of fungal allergy induced by Aspergillus fumigatus (A. fumigatus) by treatment of A. fumigatus-sensitized mice with NG-nitro-L-arginine methyl ester (L-NAME) or D-NAME (8 mg/kg; i.p.).


METHODS
Female CBA/J mice received A. fumigatus antigen dissolved in incomplete Freund's adjuvant (10 mg/100 ml i.p. and s.c.) followed 2 weeks later by A. fumigatus antigens (20 mg; i.n.) and a subsequent i.t. challenge 4 days later. Airway physiology and inflammation were examined (24 to 72 h) following i.t. challenge.


RESULTS
L-NAME-treated mice had lower lung nitrite levels 24 h after A. fumigatus challenge, but higher airway hyperresponsiveness and inflammation compared to D-NAME controls. Airway inflammation in the L-NAME treatment group (72 h) was characterized by a greater bronchoalveolar lavage (BAL), peribronchial eosinophilia and augmented levels of CC chemokines compared to controls.


CONCLUSIONS
These findings suggest that nitric oxide is an important modulator of airway hyperresponsiveness, inflammation and C-C chemokine generation during allergic airway responses to A. fumigatus.
Blease
K
K
Department of Pathology, University of Michigan Medical School, Ann Arbor 48109-0602, USA.
Kunkel
S L
SL
Hogaboam
C M
CM
D000818:Animals; D001232:Aspergillus fumigatus / Q000276:immunology*; D001249:Asthma / Q000503:physiopathology*; D016535:Bronchial Hyperreactivity / Q000209:etiology*; D019742:Chemokines, CC / Q000096:biosynthesis*; D004802:Eosinophilia / Q000209:etiology*; D005260:Female; D007073:Immunoglobulin E / Q000097:blood; D051379:Mice; D008808:Mice, Inbred CBA; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*
D019742:Chemokines, CC; D009569:Nitric Oxide; D007073:Immunoglobulin E; D019331:NG-Nitroarginine Methyl Ester