5-oxo-6,8,11,14-eicosatetraenoic acid is a potent stimulator of L-selectin shedding, surface expression of CD11b, actin polymerization, and calcium mobilization in human eosinophils.
5-oxo-6,8,11,14-eicosatetraenoic acid (5-oxo-ETE) is a metabolite of arachidonic acid formed by the oxidation of 5-hydroxy-6,8,11, 14-eicosatetraenoic acid by a highly specific dehydrogenase. 5-oxo-ETE is a chemoattractant for both neutrophils and eosinophils. Although it is not as effective as leukotriene B4 (LTB4) and platelet-activating factor (PAF) in stimulating neutrophil migration, we found that it is considerably more active than these and a variety of other lipid mediators as an eosinophil chemoattractant. Moreover, low concentrations of 5-oxo-ETE appear to enhance the responsiveness of these cells to PAF. The objectives of the current investigation were to identify rapid responses induced in eosinophils by 5-oxo-ETE that might be related to the infiltration of these cells into tissues. We found that 5-oxo-ETE is more effective than PAF and LTB4 in inducing both L-selectin shedding and actin polymerization in human eosinophils, whereas PAF is the most active of these mediators in stimulating calcium mobilization. The complementary effects of 5-oxo-ETE and PAF on actin polymerization and calcium mobilization may explain their synergistic effect on eosinophil migration. 5-oxo-ETE and PAF were equipotent in stimulating the surface expression of the beta2-integrin CD11b, but were slightly less potent than LTB4. 5-oxo-ETE- induced actin polymerization was subject to homologous but not heterologous desensitization. It was not prevented by incubation of eosinophils with inhibitors of protein kinase C (staurosporine), mitogen-activated protein kinase kinase (PD98059), or phosphatidylinositol-3-kinase (wortmannin). In conclusion, 5-oxo-ETE is a potent activator of human eosinophils and may be an important regulator of tissue infiltration of these cells.
Powell
W S
WS
Department of Medicine, McGill University, Montreal, Quebec, Canada. Bill@Meakins.LAN.McGill.ca
Gravel
S
S
Halwani
F
F
D000199:Actins / Q000097:blood*; D001095:Arachidonic Acids / Q000494:pharmacology*; D002118:Calcium / Q000097:blood; D002630:Chemotactic Factors / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004804:Eosinophils / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D019041:L-Selectin / Q000097:blood*; D007975:Leukotriene B4 / Q000494:pharmacology; D016177:Macrophage-1 Antigen / Q000097:blood*; D010972:Platelet Activating Factor / Q000494:pharmacology; D011108:Polymers / Q000378:metabolism; D047428:Protein Kinase Inhibitors
D000199:Actins; D001095:Arachidonic Acids; D002630:Chemotactic Factors; D004791:Enzyme Inhibitors; D016177:Macrophage-1 Antigen; D010972:Platelet Activating Factor; D011108:Polymers; D047428:Protein Kinase Inhibitors; C080828:5-oxo-6,8,11,14-eicosatetraenoic acid; D019041:L-Selectin; D007975:Leukotriene B4; D002118:Calcium