Differences in the metabolism of eicosatetraenoic (20:4( n − 6)), tetracosatetraenoic (24:4( n − 6)) and triacontatetraenoic (30:4( n − 6)) acids in human neutrophils

Abstract

The metabolism of [1- 14C]eicosatetraenoic (arachidonic, 20:4( n − 6)), [1- 14C]tetracosatetraenoic (24:4( n − 6)) and [1- 14C]triacontatetraenoic (30:4( n − 6)) acids was studied in intact human neutrophils. [1- 14C]20:4( n − 6) and [1- 14C]24:4( n − 6) were efficiently taken up by the neutrophils, esterified into neutral lipids and phospholipids, and elongated by up to four carbon units. In contrast, [1- 14C]30:4(n − 6) was poorly incorporated into the cells and remained predominantly in the original unesterified form. The [1- 14C]tetraenoic fatty acids were mainly esterified into triacylglycerol, suggesting that this lipid class is important in the intracellular trafficking of polyunsaturated fatty acids. The leukocytes demonstrated a low capacity to β-oxidize and desaturate the fatty acid substrates. In the presence of calcium ionophore A23187 the neutrophils converted [1- 14C]20:4( n − 6) to a variety of radiolabelled oxygenated fatty acid derivatives including prostaglandins, thromboxanes, mono- and dihydroxylated fatty acids and leukotrienes. The major eicosanoid products were 5-monohydroxy-20:4( n − 6) and leukotriene B 4. In contrast, [1- 14C]24:4( n − 6) was metabolized to radiolabelled monohydroxylated fatty acids (predominantly the 9-hydroxy positional isomer) but not to other lipoxygenase or cyclooxygenase products by the calcium ionophore-stimulated cells. Negligible oxygenated fatty acid compounds were formed from [1- 14C]30:4( n − 6), indicating that it is a poor substrate for the neutrophil cyclooxygenase and lipoxygenase enzymes.