Dysregulated synthesis of protectin D1 in eosinophils from patients with severe asthma.
J Allergy Clin Immunol
; 131(2): 353-60.e1-2, 2013 Feb.
Article
en En
| MEDLINE
| ID: mdl-23006546
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.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Asma
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Ácidos Docosahexaenoicos
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Eosinófilos
Tipo de estudio:
Observational_studies
Límite:
Adult
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Aged
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Female
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Humans
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Male
Idioma:
En
Año:
2013
Tipo del documento:
Article