ABSTRACT
In many animal tissues and cells, linoleic acid (18:2n-6) is converted to arachidonic acid (20:4n-6) by an alternating sequence of ∆6-desaturation, chain elongation and ∆5-desaturation, in which hydrogen atoms are selectively removed to create new double bonds and two carbon atoms are then added to lengthen the fatty acid chain (1). Reports by Chapkin et al. (2) have demonstrated that peritoneal macrophages lack ∆6desaturase activity, the enzyme responsible for the conversion of 18:2n-6 into γlinolenic acid (18:3n-6, GLA). This observation suggests that the availability of macrophage 20:4n-6 cannot be modulated at the level of local synthesis from 18:2n6, its major dietary essential fatty acid antecedent. Recently, Chapkin et al. (3) have shown that peritoneal macrophages in vitro can synthesize low levels of 20:4n-6 from dihomo-γ-linolenic acid 20:3n-6, and therefore possess modest ∆5-desaturase activity. In addition, the presence of elongase activity capable of converting 18:2n-6 into 20:2n-6, 20:3n-6 into 22:3n-6, and 20:4n-6 into 22:4n-6 was noted. Although the significance of the extensive elongation (two-carbon atom chain lengthening) of polyunsaturated fatty acids (PUFAs), by macrophages in vitro remains nebulous, the pathway may serve to control the level of potential inhibitor(s) of 20:4n-6 metabolism (4). An evaluation of macrophage PUFA metabolism in vivo has also demonstrated the Presence of an active long-chain PUFA elongase. In these studies, we demonstrated that the total phospholipid 20:3n-6/20:4n-6 ratio was elevated significantly (P < 0.05) in animals fed a GLA-rich diet (5,6). This ratio was highest in the macrophage relative to the liver, spleen, and lung. Collectively, these results clearly show that the macrophage is capable of elongating GLA into 20:3n-6 and that the ∆5-desaturase, the enzyme catalyzing the transformation of 20:3n-6 into 20:4n-6, is rate limiting. The striking elevation of macrophage phospholipid 20:3n-6 levels is of particular interest because this trienoic fatty acid can serve as a precursor for the biosynthesis of eicosanoids which possess anti-inflammatory, anti-thrombotic and potent pharmacodynamic properties (7-9).
