NO chemical events in the human airway during the immediate and late antigen-induced asthmatic response.
A wealth of evidence supports increased NO (NO.) in asthma, but its roles are unknown. To investigate how NO participates in inflammatory airway events in asthma, we measured NO. and NO. chemical reaction products [nitrite, nitrate, S-nitrosothiols (SNO), and nitrotyrosine] before, immediately and 48 h after bronchoscopic antigen (Ag) challenge of the peripheral airways in atopic asthmatic individuals and nonatopic healthy controls. Strikingly, NO(3)(-) was the only NO. derivative to increase during the immediate Ag-induced asthmatic response and continued to increase over 2-fold at 48 h after Ag challenge in contrast to controls [P < 0.05]. NO(2)(-) was not affected by Ag challenge at 10 min or 48 h after Ag challenge. Although SNO was not detectable in asthmatic airways at baseline or immediately after Ag, SNO increased during the late response to levels found in healthy controls. A model of NO. dynamics derived from the current findings predicts that NO. may have harmful effects through formation of peroxynitrite, but also subserves an antioxidant role by consuming reactive oxygen species during the immediate asthmatic response, whereas nitrosylation during the late asthmatic response generates SNO, safe reservoirs for removal of toxic NO. derivatives.
Dweik
R A
RA
Department of Pulmonary and Critical Care Medicine, Cleveland Clinic Foundation, Lerner Research Institute, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
Comhair
S A
SA
Gaston
B
B
Thunnissen
F B
FB
Farver
C
C
Thomassen
M J
MJ
Kavuru
M
M
Hammel
J
J
Abu-Soud
H M
HM
Erzurum
S C
SC
D000328:Adult; D000941:Antigens / Q000276:immunology*; D001249:Asthma / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D001980:Bronchi / Q000378:metabolism* / Q000503:physiopathology; D001992:Bronchoalveolar Lavage Fluid; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism*; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism
D000941:Antigens; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine