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Allergic Asthmatics...
Allergic Asthmatics Show Divergent Lipid Mediator Profiles from Healthy Controls Both at Baseline and following Birch Pollen Provocation
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- Lundstrom, Susanna L. (författare)
- Karolinska Institutet
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- Yang, Jun (författare)
- University of California, USA
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- Kallberg, Henrik J. (författare)
- Karolinska Institutet, Sweden
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- Thunberg, Sarah, 1976- (författare)
- Karolinska Institutet
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- Gafvelin, Guro (författare)
- Karolinska Institutet
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- Haeggstrom, Jesper Z. (författare)
- Karolinska Institutet
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- Gronneberg, Reidar (författare)
- Karolinska Institutet
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- Grunewald, Johan (författare)
- Karolinska Institutet
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- van Hage, Marianne (författare)
- Karolinska Institutet
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- Hammock, Bruce D. (författare)
- University of California, USA
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- Eklund, Anders (författare)
- Karolinska Institutet
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- Wheelock, Asa M. (författare)
- Karolinska Institutet
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- Wheelock, Craig E. (författare)
- Karolinska Institutet
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(creator_code:org_t)
- 2012-03-15
- 2012
- Engelska.
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:3
- Relaterad länk:
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https://doi.org/10.1...
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https://journals.plo...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine (hsv//eng)
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Lundstrom, Susan ...
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Yang, Jun
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Kallberg, Henrik ...
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Thunberg, Sarah, ...
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Gafvelin, Guro
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Haeggstrom, Jesp ...
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Gronneberg, Reid ...
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Grunewald, Johan
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van Hage, Marian ...
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Hammock, Bruce D ...
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Eklund, Anders
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Wheelock, Asa M.
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Wheelock, Craig ...
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