5-OXO-EICOSATETRAENOATE IS A BROADLY ACTIVE, EOSINOPHIL-SELECTIVE STIMULUS FOR HUMAN GRANULOCYTES

5-Oxo-eicosatetraenoate (5-oxoETE) is gaining recognition as a chemota ctic factor for eosinophilic (Eo) as well as neutrophilic (Neu) polymo rphonuclear leukocytes. We found that the eicosanoid was far stronger than C5a, platelet-activating factor (PAF), leukotriene B-4 (LTB(4)), or FMLP in stimulating Eo chemotaxis. Moreover, it had weak intrinsic degranulating effects on otherwise unstimulated Eo, produced prominent degranulation responses in Eo primed by granulocyte-macrophage CSF, a nd enhanced the Eo-degranulating potencies of PAF, C5a, LTB(4), and FM LP by up to 10,000-fold. tow picomolar levels of 5-oxoETE also induced Eo to activate mitogen-activated protein kinases (MAPKs), as defined by shifts in the electrophoretic mobility and tyrosine phosphorylation of two immunodetectable proteins, p44 and p42. 5-OxoETE was greater t han or equal to 100-fold weaker or unable to stimulate any of these re sponses in Neu. Finally, 5-oxo-15-hydroxy-ETE and 5-hydroxy-ETE activa ted both cell types, but were weaker than 5-oxoETE and had Eo/Neu pote ncy ratios approaching unity. 5-OxoETE, thus, is uniquely potent and s elective in promoting Eo not only to migrate, but also to release gran ule enzymes and activate MAPKs. By triggering MAPK activation, the eic osanoid may also influence the production of anaphylactoid lipids (e.g ., PAF), arachidonic acid metabolites, and cytokines. 5-OxoETE therefo re possesses a biologic profile well suited for mediating Eo-dominated allergic reactions in vivo.