title: Dysregulated synthesis of protectin D1 in eosinophils from patients with severe asthma.
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.
  
  
  CONCLUSIONS
  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.affiliation: Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Miyata
authors.forename: Koichi
authors.initials: K
authors.lastname: Fukunaga
authors.forename: Ryo
authors.initials: R
authors.lastname: Iwamoto
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Isobe
authors.forename: Kyoko
authors.initials: K
authors.lastname: Niimi
authors.forename: Rina
authors.initials: R
authors.lastname: Takamiya
authors.forename: Takahisa
authors.initials: T
authors.lastname: Takihara
authors.forename: Katsuyoshi
authors.initials: K
authors.lastname: Tomomatsu
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Oguma
authors.forename: Koichi
authors.initials: K
authors.lastname: Sayama
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Arai
authors.forename: Tomoko
authors.initials: T
authors.lastname: Betsuyaku
authors.forename: Makoto
authors.initials: M
authors.lastname: Arita
authors.forename: Koichiro
authors.initials: K
authors.lastname: Asano
mesh_terms: D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000378:metabolism; D001095:Arachidonic Acids / Q000378:metabolism; D001249:Asthma / Q000276:immunology / Q000378:metabolism*; D039481:CD11b Antigen / Q000378:metabolism; D016022:Case-Control Studies; D015815:Cell Adhesion Molecules / Q000378:metabolism; D054413:Chemokine CCL11 / Q000378:metabolism; D002633:Chemotaxis / Q000502:physiology; D004281:Docosahexaenoic Acids / Q000096:biosynthesis* / Q000276:immunology; D004804:Eosinophils / Q000276:immunology / Q000378:metabolism*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D019041:L-Selectin / Q000378:metabolism; D008297:Male; D009504:Neutrophils / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D001095:Arachidonic Acids; C515456:CCL11 protein, human; D039481:CD11b Antigen; D015815:Cell Adhesion Molecules; D054413:Chemokine CCL11; C509295:ITGAM protein, human; C487679:protectin D1; D013481:Superoxides; C080828:5-oxo-6,8,11,14-eicosatetraenoic acid; D019041:L-Selectin; D004281:Docosahexaenoic Acids