Ebselen is a specific inhibitor of LTB₄-mediated migration of human neutrophils

Ebselen is a seleno-organic anti-inflammatory compound with glutathione peroxidase-like activity that has the unique characteristic of mediating the isomerization of 5-HETE and LTB₄ to their biologically inactive trans isomers, both directly in fluid phase and indirectly through metabolic pathways in stimulated peripheral blood leukocytes. LTB₄ is an inflammatory mediator with potent chemotactic activity for neutrophilic leukocytes. We studied the effects of ebselen on the chemotactic and chemokinetic responses with human-blood-derived neutrophils. With the use of 120-μm-thick 5-μm-pore durapore filters and low BSA concentrations (0.05%) in the chemotaxis buffers, ebselen was evaluated for its effect on both chemotactic and chemokinetic responses to LTB₄, C5a, and fMLP. Ebselen at 3-20 μM concentrations inhibited both chemotactic and chemokinetic responses to optimal concentrations of LTB₄ without altering chemotactic responses to C5a or fMLP. Likewise, ebselen at 20 μM specifically inhibited LTB₄-stimulated transendothelial migration of neutrophils, while not altering responses to C5a nor fMLP.