NEUTROPHIL-AGGREGATING ACTIVITY OF MONOHYDROXYEICOSATETRAENOIC ACIDS

  • 1 January 1981
    • journal article
    • research article
    • Vol. 104  (1) , 55-62
Abstract
The following oxidative derivatives of arachidonic acid were prepared and assayed for their ability to aggregate cytochalasin-B-pretreated human neutrophils: 5-, 8-, 9-, 11-, 12- and 15-hydroxyeicosatetraenoic acids. The compounds were prepared by oxidation of arachidonic acid and purified by direct and reverse phase high performance liquid chromatography. Each lipid was racemic at the hydroxy residue and had a cis-trans conjugated double bond adjacent to the hydroxy residue. Except for racemization, they were identical to hydroxyeicosatetraenoic acids generated by neutrophils exposed to diverse aggregating stimuli. 15-L-Hydroxyeicosatetraenoic acid was prepared from soybean lipoxygenase. Of the 7 fatty acid preparations, only 5- and 12-hydroxyeicosatetraenoic acid aggregated the cells. The bioactions of the lipids are crucially dependent upon the position of the hydroxy residue. The 5- and 12-hydroxy derivatives were potent aggregating agents, inducing half-maximal responses at 200 and 40 nM, respectively. Their bioactions required extracellular Ca and Mg. The response to both fatty acids was effectively blocked by 3 inhibitors of cellular arachidonic acid metabolism: nordihydroguaiaretic acid, 5,8,11,14-eicosatetraynoic acid and indomethacin. The 5- and 12-hydroxyeicosatetraenoic acids may induce neutrophils to metabolize their endogenous arachidonate. The 2 hydroxy acids may be further metabolized through pathways inhibited by arachidonate antimetabolites into a final mediator of aggregate formation.

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