Neutrophil-aggregating activity of monohydroxyeicosatetraenoic acids. Am J Pathol 1981 Jul;104(1):55-62
Date
07/01/1981Pubmed ID
7258296Pubmed Central ID
PMC1903737Scopus ID
2-s2.0-0019479927 (requires institutional sign-in at Scopus site) 46 CitationsAbstract
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 cistrans conjugated double bond adjacent to the hydroxy residue. Except for racemization, therefore, they were identical to hydroxyeicosatetraenoic acids generated by neutrophils exposed to diverse aggregating stimuli. In addition, 15-L-hydroxyeicosatetraenoic acid was prepared from soybean lipoxygenase. Of these 7 fatty acid preparations, only 5- and 12-hydroxyeicosatetraenoic acid aggregated the cells. Thus, the bioactions of these 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 calcium and magnesium. And the response to both fatty acids was effectively blocked by three inhibitors of cellular arachidonic acid metabolism: nordihydroguaiaretic acid, 5,8,11,14-eicosatetraynoic acid, and indomethacin. The 5- and 12- hydroxyeicosatetraenoic acids, therefore, may induce neutrophils to metabolize their endogenous arachidonate. Alternatively, the two hydroxy acids themselves may be further metabolized through pathways inhibited by arachidonate antimetabolites into a final mediator(s) of aggregate formation.
Author List
O'Flaherty JT, Thomas MJ, Lees CJ, McCall CEAuthor
Michael J. Thomas PhD Professor in the Pharmacology and Toxicology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
12-Hydroxy-5,8,10,14-eicosatetraenoic AcidAntimetabolites
Arachidonic Acids
Cations, Divalent
Cell Aggregation
Dose-Response Relationship, Drug
Eicosanoic Acids
Neutrophils
