Dysregulated synthesis of protectin D1 in eosinophils from patients with severe asthma

• Published in: Journal of allergy and clinical immunology Vol. 131; no. 2; pp. 353 - 360.e2
• Main Authors: Miyata, Jun, MD, Fukunaga, Koichi, MD, PhD, Iwamoto, Ryo, MS, Isobe, Yosuke, MS, Niimi, Kyoko, MD, Takamiya, Rina, PhD, Takihara, Takahisa, MD, Tomomatsu, Katsuyoshi, MD, Suzuki, Yusuke, MD, Oguma, Tsuyoshi, MD, Sayama, Koichi, MD, Arai, Hiroyuki, PhD, Betsuyaku, Tomoko, MD, PhD, Arita, Makoto, PhD, Asano, Koichiro, MD
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01.02.2013; Elsevier; Elsevier Limited
• Subjects: 15-lipoxygenase; 5-oxo-eicosatetraenoic acid; Adult; Aged; Allergy and Immunology; Anti-Inflammatory Agents - metabolism; Arachidonic Acids - metabolism; Asthma; Asthma - immunology; Asthma - metabolism; Biological and medical sciences; Biosynthesis; Case-Control Studies; CCL11; CD11b Antigen - metabolism; Cell Adhesion Molecules - metabolism; Chemokine CCL11 - metabolism; Chemotaxis - physiology; Chromatography; docosahexaenoic acid; Docosahexaenoic Acids - biosynthesis; Docosahexaenoic Acids - immunology; Eosinophils - immunology; Eosinophils - metabolism; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gene expression; Humans; IL-5; Immunopathology; Inflammation - metabolism; L-Selectin - metabolism; lipid mediator; Lipids; Male; Mass spectrometry; Medical sciences; Neutrophils - metabolism; platelet-activating factor; Rodents; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Superoxides - metabolism; Fluorescein isothiocyanate; Tandem mass spectrometry; Superoxide anion; CCL11; lipid mediator; Hank's buffered salt solution; LT; Superoxide dismutase; 15-lipoxygenase; platelet-activating factor; LX; MS/MS; HETE; FITC; docosahexaenoic acid; Hydroxyeicosatetraenoic acid; O 2; Prostaglandin; Lipoxin; IL-5; SOD; Liquid chromatography; 5-oxo-eicosatetraenoic acid; Asthma; Leukotriene; PAF; LC; PG; Protectin D1; HBSS; DHA; PD1; 5-oxo-ETE; O2; Human; Immunopathology; Enzyme; Cytokine; Granulocyte; Polyunsaturated fatty acid; Lipids; Docosahexaenoic acid; n-3 fatty acid; Eosinophil; Platelet activating factor; Immunology; Interleukin 5; Oxidoreductases; Severe asthma; Lipoxygenase
• DOI: 10.1016/j.jaci.2012.07.048
• ISSN: 0091-6749

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.