CALCIUM MOBILIZATION AND RIGHT-ANGLE LIGHT SCATTER RESPONSES TO 12-OXO-DERIVATIVES OF ARACHIDONIC-ACID IN NEUTROPHILS - EVIDENCE FOR THE INVOLVEMENT OF THE LEUKOTRIENE B4 RECEPTOR

The biological activities of two carbonyl compounds derived from arachidonic acid, (5Z,8Z,10E,14Z)-12-keto-5,8,10,14-eicosatetraenoic acid (12-OxoETE) and (5Z,8Z,10E)-12-oxo-5,8,10-dodecatrienoic acid (12-OxoDTrE) were investigated. The ability of these compounds to induce 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 cytoplasic free calcium; these effects were clearly detectable at concentrations greater-than-or-equal-to 10(-8) M. Pre-exposure of neutrophils to leukotriene B4 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 B4. The carbonyl compounds also induced a decrease in right-angle light scatter and these effects were abolished by pretreatment of neutrophils with leukotriene B4. 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 B4 binding sites or a common activation sequence.