Abstract
The biological activities of two carbonyl compounds derived from arachidonic acid, (5 Z,8 Z,10 E,14 Z)-12-keto-5,8,10,14-eicosatetraenoic acid (12-OxoETE) and (5 Z,8 Z,10 E)-12-oxo-5,8,10-dodecatrienoic acid (12-OxoDTrE) were investigated. The ability of these compounds to induced a mobilization of calcium and to trigger a right-angle scatter response in isolated peripheral blood human neutrophils was determined. The two compounds induced a rapid and dose-dependent increase in the concentration of cytoplasmic free calcium; these effects were clearly detectable at concentrations ⩾10 −8 M. Pre-exposure of neutrophils to leukotriene B 4 completely abolished the calcium mobilization induced by 12-OxoDTre and 12-OxoETE, while pre-exposure of the cells to the carbonyl compounds only slightly reduced the response to subsequent stimulation of neutrophils by leukotriene B 4.The carbonyl compounds also induced a decrease in right-angle light scatter and these effects were abolished by pretreatment of neutrophils with leukotriene B 4. These data demonstrate that 12-OxoETE and 12-OxoDTrE show significant agonist activities towards human neutrophils and strongly suggest that their mechanisms of action involve the leukotriene B 4 binding sites or a common activation sequence.
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Schedule a callMore From: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research
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