title: 5-Lipoxygenase products regulate basophil functions: 5-Oxo-ETE elicits migration, and leukotriene B(4) induces degranulation.
abstract: BACKGROUND
  5-Lipoxygenase (5-LO) products have been strongly implicated in the pathogenesis of allergic diseases. In addition to their physiologic effects on residential cells, 5-LO products are capable of stimulating various eosinophil functions. However, little is known regarding the effects of 5-LO products on basophil functions.
  
  
  OBJECTIVE
  This study was designed to elucidate the effects of the main 5-LO products (ie, leukotriene [LT] B(4), LTD(4), and 5-oxo-6,8,11,14-eicosatetraenoic acid [5-oxo-ETE]), as well as their receptor expression on human basophils.
  
  
  METHODS
  We studied the effects of 5-LO products on Ca(2+) mobilization, migration, CD 11b expression, and degranulation of human basophils. Expression of the receptors for LTC(4)/D(4)/E(4) (cysteinyl leukotriene 1 [CysLT(1)] and CysLT(2)), LTB4 (BLT(1) and BLT(2)), and 5-oxo-ETE (oxoeicosanoid [OXE]) was assessed by means of real-time PCR and flow cytometry.
  
  
  RESULTS
  At the mRNA level, basophils strongly expressed OXE and predominantly expressed CysLT(1) and BLT(2). The expression level of OXE mRNA in basophils was approximately 20-fold higher than in neutrophils and similar to that in eosinophils. At the protein level, basophils expressed CysLT(1), CysLT(2), BLT(1), and OXE, but not BLT(2). All products elicited a transient increase of cytosolic calcium, with the order of magnitude being LTB(4)>5-oxo-ETE>LTD(4). 5-Oxo-ETE induced a strong basophil migratory response that was almost equivalent to that of prostaglandin D(2). LTB(4) elicited significant degranulation of IL-3-primed basophils. In contrast, no functional significance was observed for LTD(4).
  
  
  CONCLUSIONS
  Among 5-LO products, 5-oxo-ETE induces a potent basophil migratory response, and LTB(4) elicits degranulation under certain conditions. Our results strongly suggest that 5-oxo-ETE might afford opportunities for therapeutic targeting in allergic inflammation.
authors.affiliation: Department of Allergy and Rheumatology, University of Tokyo School of Medicine, Tokyo, Japan.
authors.forename: Motoyasu
authors.initials: M
authors.lastname: Iikura
authors.forename: Maho
authors.initials: M
authors.lastname: Suzukawa
authors.forename: Masao
authors.initials: M
authors.lastname: Yamaguchi
authors.forename: Takashi
authors.initials: T
authors.lastname: Sekiya
authors.forename: Akiko
authors.initials: A
authors.lastname: Komiya
authors.forename: Chitose
authors.initials: C
authors.lastname: Yoshimura-Uchiyama
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nagase
authors.forename: Kouji
authors.initials: K
authors.lastname: Matsushima
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Koichi
authors.initials: K
authors.lastname: Hirai
mesh_terms: D001094:Arachidonate 5-Lipoxygenase / Q000276:immunology / Q000378:metabolism*; D001095:Arachidonic Acids / Q000276:immunology / Q000378:metabolism*; D015549:Basophil Degranulation Test; D001491:Basophils / Q000276:immunology / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D015550:Cell Degranulation / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology*; D002630:Chemotactic Factors / Q000276:immunology / Q000378:metabolism; D015777:Eicosanoids / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D007975:Leukotriene B4 / Q000276:immunology / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D018055:Receptors, Eicosanoid / Q000276:immunology / Q000378:metabolism; D018077:Receptors, Leukotriene / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D001095:Arachidonic Acids; D002630:Chemotactic Factors; D015777:Eicosanoids; D012333:RNA, Messenger; D018055:Receptors, Eicosanoid; D018077:Receptors, Leukotriene; C080828:5-oxo-6,8,11,14-eicosatetraenoic acid; D007975:Leukotriene B4; D001094:Arachidonate 5-Lipoxygenase; D002118:Calcium