METABOLISM OF GAMMA-LINOLENIC ACID IN HUMAN NEUTROPHILS

Gammalinolenic acid (GLA), when provided as a dietary supplement, has been reported to improve clinical symptoms of several inflammatory dis orders, The goal of the current study was to examine the metabolism of GLA and its relationship to arachidonic acid (AA) in the human neutro phil, Initial studies indicated that neutrophils provided GLA in vitro rapidly elongate it (by two carbons) to dihomogammalinolenic acid (DG LA), The bulk of this newly formed DGLA is incorporated into neutral l ipids and specifically triacylglycerides, Neutrophils from volunteers supplemented with GLA as borage oil also had elevated quantities of DG LA but not GLA, when compared with neutrophils from volunteers not con suming the GLA supplement, To determine whether DGLA could be mobilize d from cellular glycerolipids, neutrophils were stimulated with ionoph ore A23187 and fatty acid levels were determined, DGLA and AA were bot h released during stimulation, and the quantities of DGLA mobilized in creased threefold after in vitro GLA supplementation. Exogenously prov ided DGLA was converted to one major metabolite during cell stimulatio n; this product migrated on reverse-phase HPLC with the 15-lipoxygenas e product, 15-hydroxy-eicosatrienoic acid (15-HETre), Both 15-HETre an d DGLA (provided exogenously) inhibited the formation of leukotriene B -4 (LTB(4)) and 20-hydroxy-leukotriene B-4 (2O-OH-LTB(4)). The IC50 fo r 15-HETre inhibition of both LTB(4) and 20-OH-LTB(4) in A23187-stimul ated neutrophils was 5 mu M. This inhibition could be reversed by remo ving the compounds from the cells, Taken together, these data reveal t hat there are enzymes within the human neutrophil that metabolize GLA or its elongation product DGLA, and that the metabolism of GLA and AA may interact at a number of critical junctures.