Differential Mobilization of the Phospholipid and Triacylglycerol Pools of Arachidonic Acid in Murine Macrophages

Abstract

Innate immune cells such as monocytes and macrophages contain high levels of arachidonic acid (AA), part of which can be mobilized during cellular activation for the formation of a vast array of bioactive oxygenated metabolites. Monocytes and macrophages present in inflammatory foci typically incorporate large amounts of AA, not only in membrane phospholipids, but also in neutral lipids such as triacylglycerol. Thus, it was of interest to investigate the metabolic fate of these two AA pools in macrophages. Utilizing a variety of radiolabeling techniques to distinguish the phospholipid and triacylglycerol pools, we show in this paper that during an acute stimulation of the macrophages with yeast-derived zymosan, the membrane phospholipid AA pool acts as the major, if not the only, source of releasable AA. On the contrary, the AA pool in triacylglycerol appears to be used at a later stage, when the zymosan-stimulated response has declined, as a source to replenish the phospholipid pools that were consumed during the activation process. Thus, phospholipids and triacylglycerol play different in roles AA metabolism and dynamics during macrophage activation.

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“…Arachidonic acid is a polyunsaturated fatty acid commonly known as a rate-limiting precursor to the synthesis of biologically active eicosanoic acids [52]. Since the intracellular availability of arachidonic acid is a bottleneck in the biosynthesis of eicosanoic acids [53], immune cells can uptake extracellular arachidonic acid to aid in the production of eicosanoic acids [53,54]. Therefore, it is plausible that arachidonic acid is being taken up by immune cells to mount an in ammatory response against the opportunistic pathogenic bacteria.…”