Document Detail


Allergen-induced impairment of bronchoprotective nitric oxide synthesis in asthma.
MedLine Citation:
PMID:  11496234     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Endogenous nitric oxide protects against airway hyperresponsiveness (AHR) to bradykinin in mild asthma, whereas AHR to bradykinin is enhanced by inhaled allergens. OBJECTIVE: Hypothesizing that allergen exposure impairs bronchoprotective nitric oxide within the airways, we studied the effect of the inhaled nitric oxide synthase (NOS) inhibitor N(G)-monomethyl-L-arginine (L-NMMA) on AHR to bradykinin before and after allergen challenge in 10 subjects with atopic asthma. METHODS: The study consisted of 3 periods (1 diluent and 2 allergen challenges). AHR to bradykinin (PD(20)BK) was examined before and 48 hours after allergen challenge, both after double-blinded pretreatment with L-NMMA or placebo. The accompanying expression of the various NOS isoforms (ecNOS, nNOS, and iNOS) was examined by means of immunohistochemistry in bronchial biopsies obtained after diluent and allergen challenge. RESULTS: After placebo, AHR to BK worsened after allergen challenge in comparison with before allergen challenge (PD(20)BK, 70.8 nmol [range, 6.3-331] and 257 nmol [35.5-2041], respectively; P =.0004). After L-NMMA, preallergen and postallergen PD(20)BK values (50.1 nmol [1.8-200] vs 52.5 nmol [6.9-204]; P =.88) were similarly reduced (P <.01) and not different from the postplacebo/postallergen value (P >.05). After allergen challenge, the intensity of staining in bronchial epithelium decreased for ecNOS (P =.03) and increased for iNOS (P =.009). These changes in immunostaining were correlated with the accompanying worsening in AHR to BK (R(s) = -0.66 and 0.71; P <.04). CONCLUSIONS: These data indicate that allergen exposure in asthma induces increased airway hyperresponsiveness to bradykinin through impaired release of bronchoprotective nitric oxide associated with downregulation of ecNOS. This suggests that new therapeutic strategies towards restoring the balance among the NOS isoforms during asthma exacerbations are warranted.
Authors:
F L Ricciardolo; M C Timmers; P Geppetti; A van Schadewijk; J J Brahim; J K Sont; H W de Gouw; P S Hiemstra; J H van Krieken; P J Sterk
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of allergy and clinical immunology     Volume:  108     ISSN:  0091-6749     ISO Abbreviation:  J. Allergy Clin. Immunol.     Publication Date:  2001 Aug 
Date Detail:
Created Date:  2001-08-09     Completed Date:  2001-09-06     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  1275002     Medline TA:  J Allergy Clin Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  198-204     Citation Subset:  AIM; IM    
Affiliation:
Department of Pulmonology, Leiden University Medical Center, The Netherlands.
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MeSH Terms
Descriptor/Qualifier:
Adult
Allergens / immunology*
Asthma / immunology*
Bradykinin / immunology*
Bronchi / immunology*
Female
Humans
Hypersensitivity, Immediate / immunology
Immunohistochemistry
Isoenzymes / isolation & purification
Male
Nitric Oxide / biosynthesis*
Nitric Oxide Synthase / isolation & purification
omega-N-Methylarginine / pharmacology
Chemical
Reg. No./Substance:
0/Allergens; 0/Isoenzymes; 10102-43-9/Nitric Oxide; 17035-90-4/omega-N-Methylarginine; 58-82-2/Bradykinin; EC 1.14.13.39/Nitric Oxide Synthase

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