Document Detail


Dysregulated synthesis of protectin D1 in eosinophils from patients with severe asthma.
MedLine Citation:
PMID:  23006546     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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.
Authors:
Jun Miyata; Koichi Fukunaga; Ryo Iwamoto; Yosuke Isobe; Kyoko Niimi; Rina Takamiya; Takahisa Takihara; Katsuyoshi Tomomatsu; Yusuke Suzuki; Tsuyoshi Oguma; Koichi Sayama; Hiroyuki Arai; Tomoko Betsuyaku; Makoto Arita; Koichiro Asano
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-9-21
Journal Detail:
Title:  The Journal of allergy and clinical immunology     Volume:  -     ISSN:  1097-6825     ISO Abbreviation:  J. Allergy Clin. Immunol.     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-9-25     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  1275002     Medline TA:  J Allergy Clin Immunol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.
Affiliation:
Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan.
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