TY - JOUR
T1 - Dysregulated synthesis of protectin D1 in eosinophils from patients with severe asthma
AU - Miyata, Jun
AU - Fukunaga, Koichi
AU - Iwamoto, Ryo
AU - Isobe, Yosuke
AU - Niimi, Kyoko
AU - Takamiya, Rina
AU - Takihara, Takahisa
AU - Tomomatsu, Katsuyoshi
AU - Suzuki, Yusuke
AU - Oguma, Tsuyoshi
AU - Sayama, Koichi
AU - Arai, Hiroyuki
AU - Betsuyaku, Tomoko
AU - Arita, Makoto
AU - Asano, Koichiro
PY - 2013/2
Y1 - 2013/2
N2 - 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.
AB - 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.
KW - 15-lipoxygenase
KW - 5-oxo-eicosatetraenoic acid
KW - Asthma
KW - CCL11
KW - IL-5
KW - docosahexaenoic acid
KW - lipid mediator
KW - platelet-activating factor
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U2 - 10.1016/j.jaci.2012.07.048
DO - 10.1016/j.jaci.2012.07.048
M3 - Article
C2 - 23006546
AN - SCOPUS:84873408118
SN - 0091-6749
VL - 131
SP - 353-360.e2
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
IS - 2
ER -