Abstract | BACKGROUND: 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.
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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 |
Journal | The Journal of allergy and clinical immunology
(J Allergy Clin Immunol)
Vol. 131
Issue 2
Pg. 353-60.e1-2
(Feb 2013)
ISSN: 1097-6825 [Electronic] United States |
PMID | 23006546
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved. |
Chemical References |
- Anti-Inflammatory Agents
- Arachidonic Acids
- CCL11 protein, human
- CD11b Antigen
- Cell Adhesion Molecules
- Chemokine CCL11
- ITGAM protein, human
- protectin D1
- Superoxides
- 5-oxo-6,8,11,14-eicosatetraenoic acid
- L-Selectin
- Docosahexaenoic Acids
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Topics |
- Adult
- Aged
- Anti-Inflammatory Agents
(metabolism)
- Arachidonic Acids
(metabolism)
- Asthma
(immunology, metabolism)
- CD11b Antigen
(metabolism)
- Case-Control Studies
- Cell Adhesion Molecules
(metabolism)
- Chemokine CCL11
(metabolism)
- Chemotaxis
(physiology)
- Docosahexaenoic Acids
(biosynthesis, immunology)
- Eosinophils
(immunology, metabolism)
- Female
- Humans
- Inflammation
(metabolism)
- L-Selectin
(metabolism)
- Male
- Neutrophils
(metabolism)
- Superoxides
(metabolism)
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