Prostaglandin biosynthesis in pulmonary macrophages.
Cultured rabbit alveolar macrophages, prelabeled with 14C-arachidonic acid (AA), released into the medium a trace amount of labeled prostaglandins (PG) as well as their precursor, AA. Phagocytosis of zymosan, heat-killed Staphylococcus, or bacille Calmette-Guérin (BCG) increased the AA and PG release to 2--2.5 times control values. The released PGs consisted of PGE2, D2, F2 alpha, and 6-keto F1 alpha. Phagocytosis of latex particles had no effect on PG release. Indomethacin inhibited release of PGs but did not affect AA release at low doses. Analysis of the cellular lipids showed that zymosan decreased the radioactive label in phosphatidylcholine (PC), but not in other phospholipids or neutral lipids, suggesting that PC is the main source of AA for PG synthesis in pulmonary macrophages. Cytochalasin B (CB) at phagocytosis-inhibiting doses or below, markedly increased PG synthesis by zymosan-treated macrophages. These data suggest that PG release is not dependent on engulfment of the particles. Phagocytosis of zymosan (but not latex) also resulted in the release of two lysosomal enzymes, acid phosphatase and beta-glucuronidase, which appeared temporally associated with the release of PGs (but not to phagocytosis). Furthermore, CB augmented the zymosan-stimulated release of these enzymes at the same doses stimulating PG synthesis. However, indomethacin, at a dose completely inhibiting PG synthesis, failed to block lysosomal enzyme release. Thus, the coincidental release of PGs and lysosomal enzymes is not the result of a regulatory role of PGs in the release of lysosomal enzymes, but probably is the result of a common pathway of stimulation. (Am J Pathol 97:137--148, 1979).
D000818:Animals; D002478:Cells, Cultured; D007213:Indomethacin / Q000494:pharmacology; D007840:Latex; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D008863:Microspheres; D010587:Phagocytosis; D011453:Prostaglandins / Q000096:biosynthesis*; D011650:Pulmonary Alveoli / Q000166:cytology; D011817:Rabbits; D015054:Zymosan
D007840:Latex; D011453:Prostaglandins; D015054:Zymosan; D007213:Indomethacin