Arachidonic acid metabolism by lipoxygenase in leukocytes of different species and the chemokinetic activity of some products (Abstract)

Abstract

Mono-hydroxy acids derived from arachidonic acid (AA) via the lipoxygenase pathway have been reported to be chemokinetic and chemotatic for human leukocytes, 5-hydroxyeicosatetraenoic acid (5-HETE) being the most potent¹. In the present study we have investigated the metabolism of AA in rat and rabbit peritoneal exudate cells (PEC) and in human leukocytes together with the chemokinetic activity of the products for each species. Following extraction and purification, the metabolites formed during incubation of [¹⁴C]AA with rat and rabbit PEC and human peripheral blood leukocytes were identified by UV spectrophotometry and gas chromatography mass spectrometry. Lipoxygenase activity was detected in the leukocytes of all three species but the end products varied. Normal rat PEC produced a mixture of 11- and 12-HETE while those of the rabbit formed predominantly 5-HETE and lesser amounts of 11- and 12-HETE. Human cells were also able to biosynthesize a mixture of 5-, 11- and 12-HETE. The relative chemokinetic potencies of 5-, 12- and 15-HETE and the analogous hydroperoxy acids were examined in an agarose micro-drop assay² using rat and rabbit PEC and human peripheral leukocytes. All the acids studied were active on rabbit PEC in concentrations between 0.1 and 3.2 µg/ml with a rank order of 12-HETE > 15-HPETE > 15-HETE > AA = 5-HPETE > 5-HETE.