title: 5-Oxo-6,8,11,14-eicosatetraenoic acid induces important eosinophil transmigration through basement membrane components: comparison of normal and asthmatic eosinophils.
abstract: Basement membrane transmigration is an important step in tissue recruitment of eosinophils into inflamed tissue. Recent reports showed that this phenomenon is modulated by platelet-activating factor (PAF) in combination with cytokines and proteinases. We investigated the in vitro efficacy of 5-oxo-6,8,11, 14-eicosatetraenoic acid (5-oxo-ETE), a metabolite of arachidonic acid and known as a potent eosinophil chemotactic factor, in promoting the transmigration of blood eosinophils from normal and asthmatic subjects through a Matrigel basement membrane. 5-Oxo-ETE proved to be a more potent (> 10-fold) inducer of eosinophil transmigration than PAF, and this effect was similar in cells from normal and asthmatic subjects (82.0 +/- 3.7% and 88.1 +/- 3.7%, respectively). Moreover, 5-oxo-ETE was active in the absence of interleukin (IL)-5, although this cytokine amplified the effect of 5-oxo-ETE from 61.3 +/- 3.3% to 92.8 +/- 1.8% (p = 0.003). The membrane receptor for urokinase plasminogen activator (CD87), a serine protease, was observed on eosinophils, and its expression was increased by IL-5. The inhibition of both metalloproteinases (MMP) and plasmin/plasminogen complex with inhibitor or monoclonal antibodies decreased cell transmigration by about 50%. Combination of an MMP inhibitor with anti-CD87 antibodies had no additive effect. These data show that 5-oxo-ETE is an efficient promoter of eosinophil transmigration in vitro, and is much more potent in this respect than PAF. The data suggest that 5-oxo-ETE could play an important role in eosinophil recruitment in vivo. Moreover, they demonstrate that in addition to MMP, the plasmin/plasminogen system could be involved in eosinophil transmigration.
authors.affiliation: Unité de Recherche, Centre de Pneumologie de l'Hôpital Laval, Université Laval, Sainte-Foy, Québec, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Guilbert
authors.forename: C
authors.initials: C
authors.lastname: Ferland
authors.forename: M
authors.initials: M
authors.lastname: Bossé
authors.forename: N
authors.initials: N
authors.lastname: Flamand
authors.forename: S
authors.initials: S
authors.lastname: Lavigne
authors.forename: M
authors.initials: M
authors.lastname: Laviolette
mesh_terms: D000328:Adult; D001095:Arachidonic Acids / Q000494:pharmacology*; D001249:Asthma / Q000097:blood / Q000378:metabolism*; D001485:Basement Membrane / Q000502:physiology*; D002465:Cell Movement / Q000187:drug effects; D002630:Chemotactic Factors / Q000494:pharmacology*; D017364:Collagenases / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D004804:Eosinophils / Q000187:drug effects*; D005260:Female; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D015848:Interleukin-5 / Q000494:pharmacology; D008297:Male; D020780:Matrix Metalloproteinase 9; D061965:Matrix Metalloproteinase Inhibitors; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000276:immunology / Q000378:metabolism; D055293:Receptors, Urokinase Plasminogen Activator; D013997:Time Factors; D014568:Urokinase-Type Plasminogen Activator / Q000494:pharmacology
chemical_list: D001095:Arachidonic Acids; C108282:BB 3103; D002630:Chemotactic Factors; D006877:Hydroxamic Acids; D015848:Interleukin-5; D061965:Matrix Metalloproteinase Inhibitors; C524898:PLAUR protein, human; D010972:Platelet Activating Factor; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; C080828:5-oxo-6,8,11,14-eicosatetraenoic acid; D014568:Urokinase-Type Plasminogen Activator; D017364:Collagenases; D008666:Metalloendopeptidases; D020780:Matrix Metalloproteinase 9