Allergic Asthmatics Show Divergent Lipid Mediator Profiles from Healthy Controls Both at Baseline and following Birch Pollen Provocation

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Fältnamn	Indikatorer	Metadata
000		04947naa a2200505 4500
001		oai:DiVA.org:kth-205251
003		SwePub
008		170411s2012 \| \|\|\|\|\|\|\|\|\|\|\|000 \|\|eng\|
009		oai:prod.swepub.kib.ki.se:124513636
024	7	a https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-2052512 URI
024	7	a https://doi.org/10.1371/journal.pone.00337802 DOI
024	7	a http://kipublications.ki.se/Default.aspx?queryparsed=id:1245136362 URI
040		a (SwePub)kthd (SwePub)ki
041		a engb eng
042		9 SwePub
072	7	a ref2 swepub-contenttype
072	7	a art2 swepub-publicationtype
100	1	a Lundstrom, Susanna L.u Karolinska Institutet4 aut
245	1 0	a Allergic Asthmatics Show Divergent Lipid Mediator Profiles from Healthy Controls Both at Baseline and following Birch Pollen Provocation
264		c 2012-03-15
264	1	b Public Library of Science (PLoS),c 2012
338		a print2 rdacarrier
500		a QC 20170419
520		a Background: Asthma is a respiratory tract disorder characterized by airway hyper-reactivity and chronic inflammation. Allergic asthma is associated with the production of allergen-specific IgE and expansion of allergen-specific T-cell populations. Progression of allergic inflammation is driven by T-helper type 2 (Th2) mediators and is associated with alterations in the levels of lipid mediators. Objectives: Responses of the respiratory system to birch allergen provocation in allergic asthmatics were investigated. Eicosanoids and other oxylipins were quantified in the bronchoalveolar lumen to provide a measure of shifts in lipid mediators associated with allergen challenge in allergic asthmatics. Methods: Eighty-seven lipid mediators representing the cyclooxygenase (COX), lipoxygenase (LOX) and cytochrome P450 (CYP) metabolic pathways were screened via LC-MS/MS following off-line extraction of bronchoalveolar lavage fluid (BALF). Multivariate statistics using OPLS were employed to interrogate acquired oxylipin data in combination with immunological markers. Results: Thirty-two oxylipins were quantified, with baseline asthmatics possessing a different oxylipin profile relative to healthy individuals that became more distinct following allergen provocation. The most prominent differences included 15-LOX-derived omega-3 and omega-6 oxylipins. Shared-and-Unique-Structures (SUS)-plot modeling showed a correlation (R-2 = 0.7) between OPLS models for baseline asthmatics ((RY)-Y-2[cum] = 0.87, Q(2)[cum] = 0.51) and allergen-provoked asthmatics ((RY)-Y-2[cum] = 0.95, Q(2)[cum] = 0.73), with the majority of quantified lipid mediators and cytokines contributing equally to both groups. Unique structures for allergen provocation included leukotrienes (LTB4 and 6-trans-LTB4), CYP-derivatives of linoleic acid (epoxides/diols), and IL-10. Conclusions: Differences in asthmatic relative to healthy profiles suggest a role for 15-LOX products of both omega-6 and omega-3 origin in allergic inflammation. Prominent differences at baseline levels indicate that non-symptomatic asthmatics are subject to an underlying inflammatory condition not observed with other traditional mediators. Results suggest that oxylipin profiling may provide a sensitive means of characterizing low-level inflammation and that even individuals with mild disease display distinct phenotypic profiles, which may have clinical ramifications for disease.
650	7	a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaper0 (SwePub)3012 hsv//swe
650	7	a MEDICAL AND HEALTH SCIENCESx Basic Medicine0 (SwePub)3012 hsv//eng
700	1	a Yang, Junu University of California, USA4 aut
700	1	a Kallberg, Henrik J.u Karolinska Institutet, Sweden4 aut
700	1	a Thunberg, Sarah,d 1976-u Karolinska Institutet4 aut0 (Swepub:kth)u1rw1xrj
700	1	a Gafvelin, Gurou Karolinska Institutet4 aut
700	1	a Haeggstrom, Jesper Z.u Karolinska Institutet4 aut
700	1	a Gronneberg, Reidaru Karolinska Institutet4 aut
700	1	a Grunewald, Johanu Karolinska Institutet4 aut
700	1	a van Hage, Marianneu Karolinska Institutet4 aut
700	1	a Hammock, Bruce D.u University of California, USA4 aut
700	1	a Eklund, Andersu Karolinska Institutet4 aut
700	1	a Wheelock, Asa M.u Karolinska Institutet4 aut
700	1	a Wheelock, Craig E.u Karolinska Institutet4 aut
710	2	a Karolinska Institutetb University of California, USA4 org
773	0	t PLOS ONEd : Public Library of Science (PLoS)g 7:3q 7:3x 1932-6203
856	4	u https://doi.org/10.1371/journal.pone.0033780y Fulltext
856	4	u https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0033780&type=printable
856	4 8	u https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-205251
856	4 8	u https://doi.org/10.1371/journal.pone.0033780
856	4 8	u http://kipublications.ki.se/Default.aspx?queryparsed=id:124513636

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Av författaren/redakt...: Lundstrom, Susan ...; Yang, Jun; Kallberg, Henrik ...; Thunberg, Sarah, ...; Gafvelin, Guro; Haeggstrom, Jesp ...; visa fler...; Gronneberg, Reid ...; Grunewald, Johan; van Hage, Marian ...; Hammock, Bruce D ...; Eklund, Anders; Wheelock, Asa M.; Wheelock, Craig ...; visa färre...

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