5-Oxo-6,8,11,14-Eicosatetraenoic Acid Induces Important Eosinophil Transmigration through Basement Membrane Components

• DOI: 10.1165/ajrcmb.21.1.3517
• Publication Date: 2013-04-04T01:56:28Z
• Authors: Martin Guilbert; Claudine Ferland; Marc Bossé; Nicolas Flamand; Sophie Lavigne; Michel Laviolette
• Keywords: Adult; Male; 0303 health sciences; Chemotactic Factors; Dose-Response Relationship, Drug; Metalloendopeptidases; Receptors, Cell Surface; Arachidonic Acids; Matrix Metalloproteinase Inhibitors; Hydroxamic Acids; Asthma; Basement Membrane; Receptors, Urokinase Plasminogen Activator; 3. Good health; Eosinophils; 03 medical and health sciences; Matrix Metalloproteinase 9; Cell Movement; Humans; Female; Collagenases; Interleukin-5; Platelet Activating Factor

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.