Abstract | BACKGROUND: METHODS: Peripheral blood eosinophils were isolated from four groups of subjects: healthy volunteers (HV; n = 8), mild asthma (MA; n = 8), severe asthma (SA; n = 9) and AIA (n = 7). In the absence or presence of lysine-aspirin, eosinophils were stimulated with arachidonic acid or calcium ionophore to trigger the 15-lipoxygenase-1 (15-LO) and 5-lipoxygenase (5-LO) pathways, respectively. 15(S)-hydroxy-eicosatetraenoic acid (15-HETE) and eoxin C4 (EXC4) were measured as 15-LO products and leukotriene (LT)C4 as a product of the 5-LO pathway. RESULTS: Activated eosinophils from patients with SA and AIA produced approximately five times more 15-HETE than eosinophils from HV or MA patients. In the presence of lysine-aspirin, eosinophils from AIA, MA and SA patients generated higher levels of 15-HETE than in the absence of lysine-aspirin. Furthermore, in the presence of lysine-aspirin, formation of EXC4 was also significantly increased in eosinophils from AIA patients, and LTC4 synthesis was increased both in AIA and SA patients. CONCLUSIONS: Taken together, this study shows an increased release of the recently discovered lipid mediator EXC4, as well as the main indicator of 15-LO activity, 15-HETE, in activated eosinophils from severe and aspirin-intolerant asthmatics, and also elevated EXC4 and LTC4 formation in eosinophils from AIA patients after cellular activation in the presence of lysine-aspirin. The findings support a pathophysiological role of the 15-LO pathway in SA and AIA.
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Authors | Anna James, Kameran Daham, Linda Backman, Asa Brunnström, Tove Tingvall, Maria Kumlin, Charlotte Edenius, Sven-Erik Dahlén, Barbro Dahlén, Hans-Erik Claesson |
Journal | International archives of allergy and immunology
(Int Arch Allergy Immunol)
Vol. 162
Issue 2
Pg. 135-42
( 2013)
ISSN: 1423-0097 [Electronic] Switzerland |
PMID | 23921438
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2013 S. Karger AG, Basel. |
Chemical References |
- Hydroxyeicosatetraenoic Acids
- Leukotrienes
- eoxin C4
- Arachidonic Acid
- Leukotriene C4
- 15-hydroxy-5,8,11,13-eicosatetraenoic acid
- ALOX15 protein, human
- Arachidonate 15-Lipoxygenase
- Arachidonate 5-Lipoxygenase
- Aspirin
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Topics |
- Adult
- Arachidonate 15-Lipoxygenase
(metabolism)
- Arachidonate 5-Lipoxygenase
(metabolism)
- Arachidonic Acid
(metabolism)
- Aspirin
(adverse effects, immunology)
- Asthma, Aspirin-Induced
(immunology, metabolism)
- Eosinophils
(drug effects, metabolism)
- Female
- Humans
- Hydroxyeicosatetraenoic Acids
(metabolism)
- Leukotriene C4
(metabolism)
- Leukotrienes
(metabolism)
- Male
- Middle Aged
- Young Adult
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