RELATION OF RESPIRATORY BURST AND ARACHIDONATE METABOLISM DURING PHAGOCYTOSIS BY GUINEA-PIG ALVEOLAR MACROPHAGES

  • 1 January 1982
    • journal article
    • research article
    • Vol. 99  (6) , 908-916
Abstract
Guinea pig alveolar macrophages were stimulated with opsonized zymosan in the presence of inhibitors of arachidonic acid metabolism: ASA [acetylsalicylic acid], indomethacin and ETYA [5,8,11,14-eicosatetraynoic acid]. ASA, at concentrations as high as 60 .mu.g/ml, had no effect on O2 consumption or superoxide ion formation. Indomethacin (4 .times. 10-4 M) and ETYA (2 .times. 10-5 M) did inhibit O2 utilization and superoxide production. However, no indomethacin or ETYA inhibition of O2 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 .times. 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 [12-hydroxyeicosatetraenoic acid] on silica gel plates. Lower concentrations of ETYA (5 .times. 10-6 M), which had no effect on the respiratory burst of phagocytosing alveolar macrophages, also inhibited arachidonic acid metabolism. The inhibition of O2 consumption and superoxide production by ETYA at 2 .times. 10-5 M is apparently unrelated to inhibition of arachidonic acid metabolism. The oxygenation of arachidonic acid requires little of the O2 consumed by phagocytosing alveolar macrophages.