5-Oxo-eicosatetraenoate, a potent human neutrophil stimulus.
5-Oxo-eicosatetraenoate (5-oxoETE), a newly defined arachidonate metabolite, resembled 5-hydroxyeicosatetraenoate (5-HETE) in stimulating neutrophils to mobilize Ca2+ an in promoting PMN degranulation responses to other agents. It was, however, 10-fold stronger than 5-HETE and, like leukotriene (LT) B4, had intrinsic PMN degranulating effects. Nonetheless, 5-oxoETE and 5-HETE desensitized PMN to themselves or each other but not to LTB4; LTB4 desensitized to itself but not to 5-oxoETE or 5-HETE; and an antagonist blocked LTB4 but not 5-oxoETE or 5-HETE. 5-OxoETE and 5-HETE thus induce diverse PMN responses using a shared, down-regulatable, and receptor-like mechanism that does not involve LTB4 receptors; 5-oxoETE is the preferred natural agonist for this mechanism.
Department of Medicine, Wake Forest University Medical Center, Winston-Salem, NC 27157.
J T
JT
O'Flaherty
J
J
Cordes
J
J
Redman
M J
MJ
Thomas
D001095:Arachidonic Acids / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D015550:Cell Degranulation / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000494:pharmacology; D066298:In Vitro Techniques; D007975:Leukotriene B4 / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D013777:Tetrazoles / Q000494:pharmacology
D001095:Arachidonic Acids; D006893:Hydroxyeicosatetraenoic Acids; D013777:Tetrazoles; C080828:5-oxo-6,8,11,14-eicosatetraenoic acid; D007975:Leukotriene B4; C022022:5-hydroxy-6,8,11,14-eicosatetraenoic acid; C063823:LY 255283; D002118:Calcium