Modulatory activity of 9-hydroxy- and 9-hydroperoxy-octadecadienoic acid towards reactive oxygen species from guinea-pig pulmonary macrophages.
As guinea-pig pulmonary macrophages (PM) synthesize the linoleic acid metabolite 9-hydroxy-octadecadienoic acid (9-OH-Lin) under non-stimulated conditions in relatively large quantities, we investigated whether this product has an effect on the macrophage's own phagocytic cell function. 9-OH-Lin, and also its hydroperoxy precursor 9-hydroperoxy-octadecadienoic acid (9-OOH-Lin), influenced the generation of PM chemiluminescence, a measure of the production of reactive oxygen species. The generation of lucigenin-enhanced chemiluminescence by stimulated and non-stimulated PM was inhibited concentration-dependently. Inhibition was observed at concentrations as low as 10 nM. Since 9-OH-Lin and 9-OOH-Lin also inhibited the generation of chemiluminescence by a cell-free enzyme system, i.e. xanthine/xanthine oxidase, the inhibitory effects might represent a scavenging activity towards reactive oxygen species. 9-OH-Lin and 9-OOH-Lin did not influence other phagocytic cell functions, e.g. PM phagocytic capacity, the aggregatory response to the calcium ionophore A23187, or the release of lysosomal enzymes. The effects of 9-OH-Lin and 9-OOH-Lin could be ascribed to the hydroxy and hydroxyperoxy moiety, respectively, as evidenced by lack of effect of the native fatty acid linoleic acid. We conclude that the formation of 9-OH-Lin and 9-OOH-Lin by PM may represent a regulatory mechanism towards the cell's own activity by modulating reactive oxygen species.
Engels
F
F
Department of Veterinary Pharmacology, University of Utrecht, The Netherlands.
Henricks
P A
PA
van der Vliet
H
H
Nijkamp
F P
FP
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002449:Cell Aggregation / Q000187:drug effects; D004926:Escherichia coli; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D006168:Guinea Pigs; D006861:Hydrogen Peroxide / Q000378:metabolism*; D066298:In Vitro Techniques; D007700:Kinetics; D008041:Linoleic Acids / Q000494:pharmacology*; D044243:Linoleic Acids, Conjugated; D008163:Luminescent Measurements; D008264:Macrophages / Q000187:drug effects / Q000502:physiology*; D008297:Male; D010587:Phagocytosis / Q000187:drug effects*; D013481:Superoxides / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014969:Xanthine Oxidase / Q000378:metabolism; D015054:Zymosan / Q000494:pharmacology
D005231:Fatty Acids, Unsaturated; D008041:Linoleic Acids; D044243:Linoleic Acids, Conjugated; D013481:Superoxides; C024347:9-hydroxy-10,12-octadecadienoic acid; D000001:Calcimycin; C049606:9-hydroperoxy-11,12-octadecadienoic acid; D015054:Zymosan; D006861:Hydrogen Peroxide; D014969:Xanthine Oxidase; D013755:Tetradecanoylphorbol Acetate