Decreased phospholipase A2 activity and prostaglandin biosynthesis in Bacillus Calmette-Guérin-activated alveolar macrophages

Abstract

Alveolar macrophages from normal and BCG-infected rabbits were labelled with [14C]arachidonate and its metabolites were measured. It was found that production of both prostaglandins and 12-hydroxyeicosatetraenoic acid was diminished markedly in BCG-primed macrophages. This decrease was due partly to a depression in cyclooxygenase and lipoxygenase activity, but mainly to a decrease in arachidonic acid release, probably due to a suppression in phospholipase A2 activity. This is indicated by a consistent depression of this enzyme activity in BCG macrophage homogenates at a wide pH range, suggesting that both lysosomal an non-lysosomal phospholipases are suppressed in BCG macrophages. However, intracellular lysosomal acid phosphatase and its release were increased markedly in BCG-primed macrophages. Our previous studies have shown a close relationship between lysosomal acid hydrolase release and production of arachidonate-prostaglandins in normal macrophages. The present study shows that in activated macrophages primed by BCG, different mechanisms are operative in the control of synthesis and release of lysosomal acid hydrolases and of the phospholipase for prostaglandin production.