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Vitamin C transporters in the airways of healthy and asthmatic humans
Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
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(Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
Nationell ämneskategori
Lungmedicin och allergi
Forskningsämne
lungmedicin
Identifikatorer
URN: urn:nbn:se:umu:diva-83488OAI: oai:DiVA.org:umu-83488DiVA, id: diva2:667634
Tillgänglig från: 2013-11-27 Skapad: 2013-11-27 Senast uppdaterad: 2018-06-08Bibliografiskt granskad
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1. Allergic airway disease: studies on diesel exhaust exposures, oxylipins and antioxidants
Öppna denna publikation i ny flik eller fönster >>Allergic airway disease: studies on diesel exhaust exposures, oxylipins and antioxidants
2013 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

Allergic airway disease, i.e. allergic rhinitis (AR) and asthma, is a common health problem. The prevalence is increasing in most countries of the world. Traffic-related air pollution has been found to induce and enhance allergic airway disease, but the underlying mechanisms are not known.

Oxylipins are fatty acid metabolites, of which several have been linked to asthmatic airway inflammation. Oxylipin profiles have previously been investigated in bronchoalveolar lavage (BAL), mainly reflecting the peripheral lung, but not in bronchial wash (BW), which better reflect the proximal airways.

The airway epithelium is covered by a respiratory tract lining fluid (RTLF) The RTLF contains antioxidants to protect from oxidative stress, which may be caused by exposure to air pollution. Previous studies have reported diminished levels of the antioxidant ascorbate (vitamin C) in the RTLF of patients with asthma. Little is known about the regulation of vitamin C in the lung.

The aim of this thesis was to investigate airway inflammatory responses to diesel exhaust exposure in patients with AR and allergic asthma; to evaluate oxylipin profiles in different regions of the lung in patients with allergic asthma; and to study the distribution of vitamin C transporters in the airways of patients with allergic asthma.

Diesel exhaust (PM10 100 μg/m3 for 2 h) induced a neutrophilic airway inflammation in healthy individuals evaluated 18 h after exposure. Patients with AR and asthma did not respond with an enhanced airway inflammation. However, a small increase in myeloperoxidase was found in BAL from patients with AR, as well as decreases in epithelial tryptase and BW stem cell factor. This indicates that other mechanisms than classical inflammation are responsible for the increased sensitivity to traffic-related air pollution in patients with allergic airway disease.

Oxylipin baseline profiles differed between peripheral and proximal airways in both allergic asthmatics and healthy individuals. Total oxylipin concentrations, and five individual oxylipins, primarily from the lipoxygenase (LOX) pathway, were elevated in BW from asthmatics compared to healthy controls, supported by immunohistochemical staining of 15-LOX-1 in the bronchial epithelium. This suggests that lung compartment-specific sampling should be considered in future studies.

Sodium dependent vitamin C transporter 2 (SVCT2) was, for the first time, found present in the human lung epithelium, localised mainly within goblet cells. A negative correlation between SVCT2+ goblet cells and vitamin C suggests that these cells may play a hitherto unknown function in ascorbate re-uptake and recycling at the air-lung interface.

Ort, förlag, år, upplaga, sidor
Umeå: Umeå Universitet, 2013. s. 60
Serie
Umeå University medical dissertations, ISSN 0346-6612 ; 1609
Nyckelord
Asthma, allergic rhinits, diesel exhaust, airway inflammation, oxylipins, metabolomics, antioxidants, SVCT2, bronchoscopy
Nationell ämneskategori
Lungmedicin och allergi
Forskningsämne
lungmedicin
Identifikatorer
urn:nbn:se:umu:diva-83493 (URN)978-91-7459-749-3 (ISBN)
Disputation
2013-12-19, Hörsal B, 9 tr, Norrlands Universitetssjukhus, Umeå, 13:00 (Svenska)
Opponent
Handledare
Tillgänglig från: 2013-11-28 Skapad: 2013-11-27 Senast uppdaterad: 2018-06-08Bibliografiskt granskad

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Larsson, NirinaRankin, GregRoos-Engstrand, EsterPourazar, JamshidBehndig, Annelie

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Lungmedicin och allergi

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