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-microns-thick 5-microns-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 microM concentrations inhibited both chemotactic and chemokinetic responses to optimal concentrations of LTB4 without altering chemotactic responses to C5a or fMLP. Likewise, ebselen at 20 microM specifically inhibited LTB4-stimulated transendothelial migration of neutrophils, while not altering responses to C5a nor fMLP.
Patrick
R A
RA
CIBA-GEIGY Corporation, Pharmaceuticals Division, Department of IOE/Research, Summit, NJ 07901.
Peters
P A
PA
Issekutz
A C
AC
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001393:Azoles / Q000494:pharmacology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D015936:Complement C5a / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D054833:Isoindoles; D007975:Leukotriene B4 / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects*; D016566:Organoselenium Compounds / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001393:Azoles; D054833:Isoindoles; D016566:Organoselenium Compounds; D007975:Leukotriene B4; C042986:ebselen; D009240:N-Formylmethionine Leucyl-Phenylalanine; D015936:Complement C5a