title: Lipid mediator profiles differ between lung compartments in asthmatic and healthy humans.
abstract: Oxylipins are oxidised fatty acids that can exert lipid mediator functions in inflammation, and several oxylipins derived from arachidonic acid are linked to asthma. This study quantified oxylipin profiles in different regions of the lung to obtain a broad-scale characterisation of the allergic asthmatic inflammation in relation to healthy individuals. Bronchoalveolar lavage fluid (BALF), bronchial wash fluid and endobronchial mucosal biopsies were collected from 16 healthy and 16 mildly allergic asthmatic individuals. Inflammatory cell counts, immunohistochemical staining and oxylipin profiling were performed. Univariate and multivariate statistics were employed to evaluate compartment-dependent and diagnosis-dependent oxylipin profiles in relation to other measured parameters. Multivariate modelling showed significantly different bronchial wash fluid and BALF oxylipin profiles in both groups (R(2)Y[cum]=0.822 and Q(2)[cum]=0.759). Total oxylipin concentrations and five individual oxylipins, primarily from the lipoxygenase (LOX) pathway of arachidonic and linoleic acid, were elevated in bronchial wash fluid from asthmatics compared to that from healthy controls, supported by immunohistochemical staining of 15-LOX-1 in the bronchial epithelium. No difference between the groups was found among BALF oxylipins. In conclusion, bronchial wash fluid and BALF contain distinct oxylipin profiles, which may have ramifications for the study of respiratory diseases. Specific protocols for sampling proximal and distal airways separately should be employed for lipid mediator studies.
authors.affiliation: Division of Medicine, Umeå University, Umeå
authors.forename: Nirina
authors.initials: N
authors.lastname: Larsson
authors.forename: Susanna L
authors.initials: SL
authors.lastname: Lundström
authors.forename: Rui
authors.initials: R
authors.lastname: Pinto
authors.forename: Gregory
authors.initials: G
authors.lastname: Rankin
authors.forename: Masoumeh
authors.initials: M
authors.lastname: Karimpour
authors.forename: Anders
authors.initials: A
authors.lastname: Blomberg
authors.forename: Thomas
authors.initials: T
authors.lastname: Sandström
authors.forename: Jamshid
authors.initials: J
authors.lastname: Pourazar
authors.forename: Johan
authors.initials: J
authors.lastname: Trygg
authors.forename: Annelie F
authors.initials: AF
authors.lastname: Behndig
authors.forename: Craig E
authors.initials: CE
authors.lastname: Wheelock
authors.forename: Malin L
authors.initials: ML
authors.lastname: Nording
mesh_terms: D000293:Adolescent; D000328:Adult; D016718:Arachidonic Acid / Q000737:chemistry; D001249:Asthma / Q000378:metabolism*; D001706:Biopsy; D001992:Bronchoalveolar Lavage Fluid; D001999:Bronchoscopy; D016022:Case-Control Studies; D045853:Exhalation; D005260:Female; D005786:Gene Expression Regulation; D064368:Healthy Volunteers; D006801:Humans; D006967:Hypersensitivity / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism; D019787:Linoleic Acid / Q000737:chemistry; D008055:Lipids / Q000737:chemistry*; D008297:Male; D009569:Nitric Oxide / Q000032:analysis; D054883:Oxylipins / Q000378:metabolism; D055815:Young Adult
chemical_list: D008055:Lipids; D054883:Oxylipins; D016718:Arachidonic Acid; D009569:Nitric Oxide; D019787:Linoleic Acid