title: Allergen-induced synthesis of F(2)-isoprostanes in atopic asthmatics. Evidence for oxidant stress.
abstract: It is thought that reactive oxygen species (ROS) participate in the inflammation which characterizes asthma, but the evidence supporting this contention is incomplete. F(2)-isoprostanes (F(2)-IsoPs) are arachidonate products formed on membrane phospholipids by the action of ROS and thereby represent a quantitative measure of oxidant stress in vivo. Using a mass spectrometric assay we measured urinary release of F(2)-IsoPs in 11 patients with mild atopic asthma after inhaled allergen challenge. The excretion of F(2)-IsoPs increased at 2 h after allergen (1.5 +/- 0.2 versus 2.6 +/- 0.3 ng/mg creatinine) and remained significantly elevated in all urine collections for the 8-h period of the study (analysis of variance [ANOVA]). The measured compounds were of noncyclooxygenase origin because neither aspirin nor indomethacin given before challenge suppressed them. Urinary F(2)-IsoPs remained unchanged after inhaled methacholine challenge. In nine atopic asthmatics, F(2)-IsoPs were quantified in bronchoalveolar lavage fluid (BALF) at baseline values and in a separate segment 24 h after allergen instillation. F(2)-IsoPs were elevated late in the BALF (0.9 +/- 0.2 versus 11.4 +/- 3.0 pg /ml, baseline versus allergen, respectively, p = 0.007). The increase was inhibited by pretreatment of the subjects with inhaled corticosteroids. These findings provide a new evidence for a role for ROS and lipid peroxidation in allergen-induced airway inflammation.
authors.affiliation: Center for Lung Research and Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tenessee 37232-2650, USA. ryszard.dworski@mcmail.vanderbilt.edu
authors.forename: R
authors.initials: R
authors.lastname: Dworski
authors.forename: J J
authors.initials: JJ
authors.lastname: Murray
authors.forename: L J
authors.initials: LJ
authors.lastname: Roberts
authors.forename: J A
authors.initials: JA
authors.lastname: Oates
authors.forename: J D
authors.initials: JD
authors.lastname: Morrow
authors.forename: L
authors.initials: L
authors.lastname: Fisher
authors.forename: J R
authors.initials: JR
authors.lastname: Sheller
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D000485:Allergens; D001249:Asthma / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D001507:Beclomethasone / Q000008:administration & dosage; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D018592:Cross-Over Studies; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004311:Double-Blind Method; D005541:Forced Expiratory Volume; D005938:Glucocorticoids / Q000008:administration & dosage; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000150:complications / Q000378:metabolism; D013058:Mass Spectrometry; D016210:Methacholine Chloride; D008875:Middle Aged; D018384:Oxidative Stress; D011460:Prostaglandins F / Q000096:biosynthesis* / Q000652:urine; D017382:Reactive Oxygen Species / Q000502:physiology; D012882:Skin Tests
chemical_list: D000485:Allergens; D016861:Cyclooxygenase Inhibitors; D005938:Glucocorticoids; D011460:Prostaglandins F; D017382:Reactive Oxygen Species; D016210:Methacholine Chloride; D001507:Beclomethasone