Relation of respiratory burst and arachidonate metabolism during phagocytosis by guinea pig alveolar macrophages.
We have examined the respiratory burst and arachidonic acid oxygenation that accompany phagocytosis in macrophages. Guinea pig alveolar macrophages were stimulated with opsonized zymosan in the presence of inhibitors of arachidonic acid metabolism: ASA, indomethacin, and ETYA, ASA, at concentrations as high as 60 micrograms/ml, had no effect on either oxygen consumption or superoxide ion formation. Indomethacin (4 x 10(-4) M) and ETYA (2 x 10(-5) M) did inhibit oxygen utilization and superoxide production. However, no indomethacin or ETYA inhibition of oxygen utilization was detected in the presence of 1 mM KCN, suggesting that the inhibitable portion of the respiratory burst observed with indomethacin or ETYA was dependent on mitochondrial respiration. Further study with ETYA showed that the inhibitor at 2 x 10(-5) M had little effect on uptake of 125I-labeled zymosan but did abolish the conversion of 14C-arachidonic acid to a compound that co-migrated with authentic 12-HETE on silica gel plates. Lower concentrations of ETYA (5 x 10(-6) M), which had no effect on the respiratory burst of phagocytosing alveolar macrophages, also inhibited arachidonic acid metabolism. We conclude therefore that the inhibition of oxygen consumption and superoxide production by ETYA at 2 x 10(-5) M is unrelated to inhibition of arachidonic acid metabolism. Furthermore, the oxygenation of arachidonic acid requires little of the oxygen consumed by phagocytosing alveolar macrophages.
D015117:5,8,11,14-Eicosatetraynoic Acid / Q000494:pharmacology / Q000031:analogs & derivatives; D000818:Animals; D001095:Arachidonic Acids / Q000037:antagonists & inhibitors / Q000378:metabolism*; D001241:Aspirin / Q000494:pharmacology; D006168:Guinea Pigs; D007213:Indomethacin / Q000494:pharmacology; D008262:Macrophage Activation; D008264:Macrophages / Q000187:drug effects / Q000502:physiology*; D010101:Oxygen Consumption / Q000187:drug effects*; D010587:Phagocytosis; D013481:Superoxides / Q000378:metabolism; D015054:Zymosan / Q000494:pharmacology
D001095:Arachidonic Acids; D013481:Superoxides; D015117:5,8,11,14-Eicosatetraynoic Acid; C029510:4,7,10,13-eicosatetraynoic acid; D015054:Zymosan; D001241:Aspirin; D007213:Indomethacin