Unique aspects of the modulation of human neutrophil function by 12-L-hydroperoxy-5,8,10,14-eicosatetraenoic acid.
12-L-hydroperoxy-5,8,10,14-eicosatetraenoic acid (12-OOHETE), a labile intermediate generated by the lipoxygenation of arachidonic acid in platelets, and 12-L-hydroxy-5,8,10.14-eicosatetraenoic acid (12-OHETE), the reduction product of 12-OOHETE, were examined for their effects on human neutrophil function in vitro. 12-OOHETE elicited a maximal neutrophil chemotactic response at 4 microgram/ml, that exceeded by over 50% the maximal chemotactic response to 10-20 microgram/ml of 12-OHETE. Similarly 12-OOHETE was more potent than 12-OHETE in evoking neutrophil chemokinetic responses and in enhancing the expression of C3b receptors on neutrophils. The concentration of guanosine 3':5' cyclic monophosphate (cGMP) in neutrophils was increased to the same plateau level by 5 ng/ml of 12-OOHETE and by 50 ng/ml of 12-OHETE. Elevations in the concentration of cGMP were maintained for 30 min or longer by a single dose of 12-OOHETE, but fell between 10 and 20 min after the introduction  of 12-OHETE. The release of neutrophil lysosomal enzymes by the chemotactic fragments of C5 was augmented substantially by 12-OOHETE, while 12-OHETE had only a marginal effect. The non-chemotactic methyl ester of 12-OHETE failed to inhibit the chemotactic responses to 12-OOHETE at molar ratios that suppressed comparable response to 12-OHETE by 42-86%. Thus 12-OOHETE is more potent than 12-OHETE in the stimulation of some human neutrophil functions and in the elevation of the cellular concentration of cGMP. Furthermore, 12-OOHETE may activate neutrophils by pathways not available to 12-OHETE.
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D001095:Arachidonic Acids / Q000494:pharmacology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D003179:Complement C3b / Q000276:immunology; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D005966:Glucuronidase / Q000378:metabolism; D006801:Humans; D015289:Leukotrienes; D008054:Lipid Peroxides; D009504:Neutrophils / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D010545:Peroxides / Q000494:pharmacology*; D011951:Receptors, Complement / Q000276:immunology; D012397:Rosette Formation
D001095:Arachidonic Acids; D015289:Leukotrienes; D008054:Lipid Peroxides; D010545:Peroxides; D011951:Receptors, Complement; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; C025086:15-hydroperoxy-5,8,11,13-eicosatetraenoic acid; D003179:Complement C3b; D000242:Cyclic AMP; D005966:Glucuronidase; D006152:Cyclic GMP