5-oxo-6,8,11,14-eicosatetraenoic acid induces important eosinophil transmigration through basement membrane components - Comparison of normal and asthmatic eosinophils

Basement membrane transmigration is an important step in tissue recruitment of eosinophils into inflamed tissue. Recent reports showed that this pheno menon 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 aci d and known as a potent eosinophil chemotactic factor, in promoting the tra nsmigration of blood eosinophils from normal and asthmatic subjects through a Matrigel basement membrane. 5-Oxo-ETE proved to be a more potent (> 10-f old) inducer of eosinophil transmigration than PAF, and this effect was sim ilar 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 int erleukin (IL)-5, although this cytokine amplified the effect of 5-oxo-ETE f rom 61.3 +/- 3.3% to 92.8 +/- 1.8% (p = 0.003). The membrane receptor for u rokinase plasminogen activator (CD87), a serine protease, was observed on e osinophils, and its expression was increased by IL-5. The inhibition of bot h metalloproteinases (MMP) and plasmin/plasminogen complex with inhibitor o r monoclonal antibodies decreased cell transmigration by about 50%. Combina tion 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 trans migration in vitro, and is much more potent in this respect than PAF. The d ata suggest that 5-oxo-ETE could play an important role in eosinophil recru itment in vivo. Moreover, they demonstrate that in addition to MMP, the pla smin/plasminogen system could be involved in eosinophil transmigration.