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The influence of aspirin on release of eoxin C4, leukotriene C4 and 15-HETE, in eosinophilic granulocytes isolated from patients with asthma.

AbstractBACKGROUND:
The effect of aspirin on the release of key arachidonic acid metabolites in activated eosinophils from subjects with aspirin-intolerant asthma (AIA) has not been investigated previously, despite the characteristic eosinophilia in AIA.
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.
AuthorsAnna James, Kameran Daham, Linda Backman, Asa Brunnström, Tove Tingvall, Maria Kumlin, Charlotte Edenius, Sven-Erik Dahlén, Barbro Dahlén, Hans-Erik Claesson
JournalInternational archives of allergy and immunology (Int Arch Allergy Immunol) Vol. 162 Issue 2 Pg. 135-42 ( 2013) ISSN: 1423-0097 [Electronic] Switzerland
PMID23921438 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 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
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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