Dysregulated synthesis of protectin D1 in eosinophils from patients with severe asthma - 30/01/13
Corresponding author: Koichiro Asano, MD, Division of Pulmonary Medicine, Department of Medicine, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa 259-1193, Japan.Abstract |
Background |
Protectin D1 (PD1) is an anti-inflammatory and proresolving lipid mediator biosynthesized from the omega-3 fatty acid docosahexaenoic acid (DHA). Exogenous PD1 conferred protection against eosinophilic inflammation in animals with experimental asthma, although its endogenous cellular source and functions in human airways are of interest.
Objective |
We sought to investigate the synthesizing capacity of PD1 in eosinophils from healthy subjects and patients with severe asthma and its direct effects on eosinophil functions.
Methods |
Human eosinophil-derived metabolites of arachidonic acid and DHA were analyzed with liquid chromatography–tandem mass spectrometry–based lipidomic analysis. The biological activities of PD1 on the function of human eosinophils, including chemotaxis, adhesion molecule expressions, degranulation, superoxide anion generation, or survival, were examined.
Results |
We identified PD1 as one of the main anti-inflammatory and proresolving molecules synthesized in human eosinophils. PD1, in nanomolar concentrations, suppressed the chemotaxis induced by CCL11/eotaxin-1 or 5-oxo-eicosatetraenoic acid and modulated the expression of the adhesion molecules CD11b and L-selectin, although it had no effects on the degranulation, superoxide anion generation, or survival of the eosinophils. Compared with the cells harvested from healthy subjects, we observed a prominent decrease in the biosynthesis of PD1 by eosinophils from patients with severe asthma, even in presence of DHA.
Conclusion |
These observations are a first indication that activated human eosinophils represent a major source of PD1, which can act as a self-resolving machinery in eosinophilic inflammation, whereas the production of PD1 is impaired in patients with severe asthma.
Le texte complet de cet article est disponible en PDF.Key words : Asthma, CCL11, docosahexaenoic acid, 15-lipoxygenase, 5-oxo-eicosatetraenoic acid, IL-5, lipid mediator, platelet-activating factor
Abbreviations used : DHA, FITC, HBSS, HETE, LC, LT, LX, MS/MS, O2−, 5-oxo-ETE, PAF, PD1, PG, SOD
Plan
| Supported by a grant-in-aid for research on allergic disease and immunology from the Ministry of Health, Labor, and Welfare (to K.A.); grants-in-aid for scientific research (to K.A. and M.A.) and for the Global COE Program (Center for Human Metabolomic Systems Biology; to J.M.) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan; a grant-in-aid from the Japan Science and Technology Agency Precursory Research for Embryonic Science and Technology (PRESTO; to M.A.); and a grant-in-aid from GlaxoSmithKline. |
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| Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest. |
Vol 131 - N° 2
P. 353 - février 2013 Retour au numéro
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