Abstract
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 ω-3 and ω-6 oxylipins. Shared-and-Unique-Structures (SUS)-plot modeling showed a correlation (R 2 = 0.7) between OPLS models for baseline asthmatics (R 2Y[cum] = 0.87, Q 2[cum] = 0.51) and allergen-provoked asthmatics (R 2Y[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 (LTB 4 and 6-trans-LTB 4), 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 ω-6 and ω-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.
| Original language | English (US) |
|---|---|
| Article number | e33780 |
| Journal | PLoS One |
| Volume | 7 |
| Issue number | 3 |
| DOIs | |
| State | Published - Mar 15 2012 |
Fingerprint
ASJC Scopus subject areas
- Agricultural and Biological Sciences(all)
- Biochemistry, Genetics and Molecular Biology(all)
- Medicine(all)
Cite this
Allergic asthmatics show divergent lipid mediator profiles from healthy controls both at baseline and following birch pollen provocation. / Lundström, Susanna L.; Yang, Jun; Källberg, Henrik J.; Thunberg, Sarah; Gafvelin, Guro; Haeggström, Jesper Z.; Grönneberg, Reidar; Grunewald, Johan; van Hage, Marianne; Hammock, Bruce D.; Eklund, Anders; Wheelock, Åsa M.; Wheelock, Craig E.
In: PLoS One, Vol. 7, No. 3, e33780, 15.03.2012.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Allergic asthmatics show divergent lipid mediator profiles from healthy controls both at baseline and following birch pollen provocation
AU - Lundström, Susanna L.
AU - Yang, Jun
AU - Källberg, Henrik J.
AU - Thunberg, Sarah
AU - Gafvelin, Guro
AU - Haeggström, Jesper Z.
AU - Grönneberg, Reidar
AU - Grunewald, Johan
AU - van Hage, Marianne
AU - Hammock, Bruce D.
AU - Eklund, Anders
AU - Wheelock, Åsa M.
AU - Wheelock, Craig E.
PY - 2012/3/15
Y1 - 2012/3/15
N2 - 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 ω-3 and ω-6 oxylipins. Shared-and-Unique-Structures (SUS)-plot modeling showed a correlation (R 2 = 0.7) between OPLS models for baseline asthmatics (R 2Y[cum] = 0.87, Q 2[cum] = 0.51) and allergen-provoked asthmatics (R 2Y[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 (LTB 4 and 6-trans-LTB 4), 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 ω-6 and ω-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.
AB - 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 ω-3 and ω-6 oxylipins. Shared-and-Unique-Structures (SUS)-plot modeling showed a correlation (R 2 = 0.7) between OPLS models for baseline asthmatics (R 2Y[cum] = 0.87, Q 2[cum] = 0.51) and allergen-provoked asthmatics (R 2Y[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 (LTB 4 and 6-trans-LTB 4), 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 ω-6 and ω-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.
UR - http://www.scopus.com/inward/record.url?scp=84863272309&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84863272309&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0033780
DO - 10.1371/journal.pone.0033780
M3 - Article
C2 - 22438998
AN - SCOPUS:84863272309
VL - 7
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 3
M1 - e33780
ER -