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Asthmatics exhibit altered oxylipin profiles compared to healthy individuals after subway air exposure
Department of Medical Biochemistry and Biophysics, Division of Physiological Chemistry II, Karolinska Institutet, Stockholm, Sweden.
Division of Respiratory Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
Division of Occupational and Environmental Medicine, Department of Public Health Sciences, Karolinska Institutet, Stockholm, Sweden.
Vise andre og tillknytning
2011 (engelsk)Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 6, nr 8, s. e23864-Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Background: Asthma is a chronic inflammatory lung disease that causes significant morbidity and mortality worldwide. Air pollutants such as particulate matter (PM) and oxidants are important factors in causing exacerbations in asthmatics, and the source and composition of pollutants greatly affects pathological implications.

Objectives: This randomized crossover study investigated responses of the respiratory system to Stockholm subway air in asthmatics and healthy individuals. Eicosanoids and other oxylipins were quantified in the distal lung to provide a measure of shifts in lipid mediators in association with exposure to subway air relative to ambient air.

Methods: Sixty-four oxylipins representing the cyclooxygenase (COX), lipoxygenase (LOX) and cytochrome P450 (CYP) metabolic pathways were screened using liquid chromatography-tandem mass spectrometry (LC-MS/MS) of bronchoalveolar lavage (BAL)-fluid. Validations through immunocytochemistry staining of BAL-cells were performed for 15-LOX-1, COX-1, COX-2 and peroxisome proliferator-activated receptor gamma (PPAR gamma). Multivariate statistics were employed to interrogate acquired oxylipin and immunocytochemistry data in combination with patient clinical information.

Results: Asthmatics and healthy individuals exhibited divergent oxylipin profiles following exposure to ambient and subway air. Significant changes were observed in 8 metabolites of linoleic- and alpha-linolenic acid synthesized via the 15-LOX pathway, and of the COX product prostaglandin E(2) (PGE(2)). Oxylipin levels were increased in healthy individuals following exposure to subway air, whereas asthmatics evidenced decreases or no change.

Conclusions: Several of the altered oxylipins have known or suspected bronchoprotective or anti-inflammatory effects, suggesting a possible reduced anti-inflammatory response in asthmatics following exposure to subway air. These observations may have ramifications for sensitive subpopulations in urban areas.

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San Francisco, CA: Public Library of Science , 2011. Vol. 6, nr 8, s. e23864-
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URN: urn:nbn:se:umu:diva-47664DOI: 10.1371/journal.pone.0023864ISI: 000294676900023OAI: oai:DiVA.org:umu-47664DiVA, id: diva2:445219
Tilgjengelig fra: 2011-10-03 Laget: 2011-09-27 Sist oppdatert: 2018-06-08bibliografisk kontrollert

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