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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

2013; Karger Publishers; Volume: 162; Issue: 2 Linguagem: Inglês

10.1159/000351422

1423-0097

Anna James, Kameran Daham, Linda Backman, Åsa Brunnström, Tove Tingvall, Maria Kumlin, Charlotte Edenius, Sven‐Erik Dahlén, Barbro Dahlén, Hans‐Erik Claesson,

Drug-Induced Adverse Reactions

<b><i>Background:</i></b> 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. <b><i>Methods:</i></b> 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. <b><i>Results:</i></b> 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. <b><i>Conclusions:</i></b> 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.