NOS 1 is required for allergen-induced expression of NOS 2 in mice.
BACKGROUND
Although increased nitric oxide (NO) production in asthma is mediated largely by upregulation of the inducible form of nitric oxide synthase (iNOS, or NOS 2), some studies have suggested an important role for the usually constitutive neural NOS isoform (nNOS, or NOS 1).


OBJECTIVE
To investigate how NOS 1 may influence allergic inflammation, we used NOS 1 knockout mice and their wild-type (WT) controls.


METHODS
Mice were sensitized and challenged with ovalbumin (OVA) using a protocol known to upregulate NOS 2 in the airways.


RESULTS
In addition to expected increases in NOS 2 activity, OVA challenge led to increases in calcium-dependent NOS activity, which was accounted for by increased expression of NOS 1 at both mRNA (n = 5, p < 0.001) and protein levels (n = 5, p < 0.01). In NOS-1-deficient mice, OVA challenge induced less eosinophilia (n = 7, p < 0.05) and much less NO production (n = 10, p < 0.01) than in WT controls, reflecting not only the expected absence of NOS 1, but also lack of upregulation of NOS 2. This interaction appeared to be stimulus specific as NOS-1-deficient mice did upregulate NOS 2 following exposure to lipopolysaccharide (n = 5, p < 0.001).


CONCLUSIONS
These findings underscore the importance of NOS 1 in allergic airway inflammation and suggest a mechanism by which NOS 1 may influence overall NO production in the airways.
Iijima
Hiroaki
H
Meakins-Christie Laboratories, Respiratory Division, Department of Medicine, McGill University Health Centre, 3626 St. Urbain Street, Montréal, Quebec H2X 2P2, Canada.
Tulic
Meri K
MK
Duguet
Alexandre
A
Shan
Jichuan
J
Carbonara
Paolo
P
Hamid
Qutayba
Q
Eidelman
David H
DH
D000485:Allergens / Q000276:immunology*; D000818:Animals; D015153:Blotting, Western; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000276:immunology; D004802:Eosinophilia / Q000276:immunology; D007150:Immunohistochemistry; D007249:Inflammation / Q000276:immunology*; D008168:Lung / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000276:immunology*; D009569:Nitric Oxide / Q000032:analysis / Q000276:immunology / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology*; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D010047:Ovalbumin / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000485:Allergens; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D009569:Nitric Oxide; D010047:Ovalbumin; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; C496321:Nos1 protein, mouse; C496317:Nos2 protein, mouse