title: Elevated levels of NO are localized to distal airways in asthma.
abstract: The contribution of nitric oxide (NO) to the pathophysiology of asthma remains incompletely defined despite its established pro- and anti-inflammatory effects. Induction of the inducible nitric oxide synthase (iNOS), arginase, and superoxide pathways is correlated with increased airway hyperresponsiveness in asthmatic subjects. To determine the contributions of these pathways in proximal and distal airways, we compared bronchial wash (BW) to traditional bronchoalveolar lavage (BAL) for measurements of reactive nitrogen/oxygen species, arginase activation, and cytokine/chemokine levels in asthmatic and normal subjects. Levels of NO were preferentially elevated in the BAL, demonstrating higher level NOS activation in the distal airway compartment of asthmatic subjects. In contrast, DHE(+) cells, which have the potential to generate reactive oxygen species, were increased in both proximal and distal airway compartments of asthmatics compared to controls. Different patterns of cytokines and chemokines were observed, with a predominance of epithelial cell-associated mediators in the BW compared to macrophage/monocyte-derived mediators in the BAL of asthmatic subjects. Our study demonstrates differential production of reactive species and soluble mediators within the distal airways compared to the proximal airways in asthma. These results indicate that cellular mechanisms are activated in the distal airways of asthmatics and must be considered in the development of therapeutic strategies for this chronic inflammatory disorder.
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: John T
authors.initials: JT
authors.lastname: Anderson
authors.forename: Meiqin
authors.initials: M
authors.lastname: Zeng
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.forename: Ryan
authors.initials: R
authors.lastname: Stapley
authors.forename: Doyle Ray
authors.initials: DR
authors.lastname: Moore
authors.forename: Balachandra
authors.initials: B
authors.lastname: Chenna
authors.forename: Naomi
authors.initials: N
authors.lastname: Fineberg
authors.forename: Jaroslaw
authors.initials: J
authors.lastname: Zmijewski
authors.forename: Isam-Eldin
authors.initials: IE
authors.lastname: Eltoum
authors.forename: Gene P
authors.initials: GP
authors.lastname: Siegal
authors.forename: Amit
authors.initials: A
authors.lastname: Gaggar
authors.forename: Stephen
authors.initials: S
authors.lastname: Barnes
authors.forename: Sadanandan E
authors.initials: SE
authors.lastname: Velu
authors.forename: Victor J
authors.initials: VJ
authors.lastname: Thannickal
authors.forename: Edward
authors.initials: E
authors.lastname: Abraham
authors.forename: Rakesh P
authors.initials: RP
authors.lastname: Patel
authors.forename: Jack R
authors.initials: JR
authors.lastname: Lancaster
authors.forename: David D
authors.initials: DD
authors.lastname: Chaplin
authors.forename: Mark T
authors.initials: MT
authors.lastname: Dransfield
authors.forename: Jessy S
authors.initials: JS
authors.lastname: Deshane
mesh_terms: D000328:Adult; D000368:Aged; D001119:Arginase / Q000378:metabolism; D001249:Asthma / Q000378:metabolism* / Q000473:pathology; D001980:Bronchi / Q000378:metabolism* / Q000473:pathology*; D018893:Bronchoalveolar Lavage; D016207:Cytokines / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D016207:Cytokines; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D001119:Arginase