Enhancement of anaphylactic mediator release from guinea-pig perfused lungs by fatty acid hydroperoxides.
Fragments of chopped lung from indomethacin treated guinea-pigs had an anti-aggregating effect when added to human platelet rich plasma (PRP), probably due to the production of prostacyclin (PGI2) since the effect was inhibited by 15-hydroperoxy arachidonic acid (15-HPAA, 10 micrograms ml(-1)). Both 15-HPAA (1-20 micrograms ml(-1) min (-1)) and 13-hydroperoxy linoleic acid (13-HPLA, 20 micrograms ml(-1) min(-1)) caused a marked enhancement of the anaphylactic release of histamine, slow-reacting substance of anaphylaxis (SRS-A) and rabbit aorta contracting substance (RCS) from guinea-pig isolated perfused lungs. This enhancement was not reversed by the concomitant infusion of either PGI2 (5 micrograms ml(-1) min (-1)) or 6-oxo-prostaglandin F1alpha (6-oxo-PGF1alpha, 5 micrograms ml(-1) min(-1)). Anaphylactic release of histamine and SRS-A from guinea-pig perfused lungs was not inhibited by PGI2 (10 ng - 10 microgram ml(-1) min(-1)) but was inhibited by PGE2 (5 and 10 micrograms ml(-1) min (-1)). Antiserum raised to 5,6-dihydro prostacyclin (PGI1) in rabbits, which also binds PGI2, had no effect on the release of anaphylactic mediators. The fatty acid hydroperoxides may enhance mediator release either indirectly by augmenting thromboxane production or by a direct effect on sensitized cells. Further experiments to distinguish between these alternatives are described in the accompanying paper (27).
D000707:Anaphylaxis; D000818:Animals; D000941:Antigens; D001095:Arachidonic Acids / Q000494:pharmacology*; D011464:Epoprostenol / Q000096:biosynthesis / Q000276:immunology / Q000494:pharmacology; D006168:Guinea Pigs; D006636:Histamine Release / Q000187:drug effects*; D006801:Humans; D007106:Immune Sera / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008041:Linoleic Acids / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010477:Perfusion; D010974:Platelet Aggregation / Q000187:drug effects; D011458:Prostaglandins E / Q000494:pharmacology; D011460:Prostaglandins F / Q000494:pharmacology; D013189:SRS-A / Q000378:metabolism*; D013928:Thromboxane A2 / Q000378:metabolism
D000941:Antigens; D001095:Arachidonic Acids; D007106:Immune Sera; D008041:Linoleic Acids; D011458:Prostaglandins E; D011460:Prostaglandins F; D013189:SRS-A; D013928:Thromboxane A2; D011464:Epoprostenol; D007213:Indomethacin