Two phospholipase pools for prostaglandin synthesis in macrophages

Abstract

Macrophages in culture produce prostaglandins in response to a variety of phagocytic and non-phagocytic stimuli^1–8. As prostaglandins are not stored in cells, and mammalian cells contain very little free arachidonic acid, synthesis and release of prostaglandins depends on the release of the precursor, arachidonic acid, from cell lipids. Many agents that stimulate cell prostaglandin production act by releasing arachidonic acid⁹, presumably by activating phospholipase A₂ (refs 10, 11) or phospholipase C (refs 12, 13), depending on the cell system used. We have shown previously that rabbit alveolar macrophages secrete arachidonic acid as well as prostaglandins in response to phagocytic stimuli^2,4,6. This secretion depends not on particle attachment, but rather on interiorization of the particles⁴. Furthermore, the time course of prostaglandin and arachidonic acid secretion does not parallel that of particle engulfment per se, but of the release of lysosomal enzymes⁴, indicating that the release of arachidonate and prostaglandin is associated with the latter. We now describe experiments which suggest that these are two independent pools of phospholipases in macrophages, one in the lysosomes and one elsewhere.