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-eicosatetraeno ic 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 cytoplasmic 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.
Naccache
P H
PH
Centre de Recherche du CHUL, Sainte-Foy, Canada.
Leblanc
Y
Y
Rokach
J
J
Patrignani
P
P
Fruteau de Laclos
B
B
Borgeat
P
P
D001095:Arachidonic Acids / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D006801:Humans; D008027:Light; D009504:Neutrophils / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000378:metabolism*; D018102:Receptors, Leukotriene B4; D012542:Scattering, Radiation
C054994:12-keto-5,8,11,13-eicosatetraenoic acid; D001095:Arachidonic Acids; D011971:Receptors, Immunologic; D018102:Receptors, Leukotriene B4; D002118:Calcium