Metabolism of gammalinolenic acid in human neutrophils.
Gammalinolenic acid (GLA), when provided as a dietary supplement, has been reported to improve clinical symptoms of several inflammatory disorders. The goal of the current study was to examine the metabolism of GLA and its relationship to arachidonic acid (AA) in the human neutrophil. Initial studies indicated that neutrophils provided GLA in vitro rapidly elongate it (by two carbons) to dihomogammalinolenic acid (DGLA). The bulk of this newly formed DGLA is incorporated into neutral lipids and specifically triacylglycerides. Neutrophils from volunteers supplemented with GLA as borage oil also had elevated quantities of DGLA but not GLA, when compared with neutrophils from volunteers not consuming the GLA supplement. To determine whether DGLA could be mobilized from cellular glycerolipids, neutrophils were stimulated with ionophore A23187 and fatty acid levels were determined. DGLA and AA were both released during stimulation, and the quantities of DGLA mobilized increased threefold after in vitro GLA supplementation. Exogenously provided DGLA was converted to one major metabolite during cell stimulation; this product migrated on reverse-phase HPLC with the 15-lipoxygenase product, 15-hydroxy-eicosa-trienoic acid (15-HETre). Both 15-HETre and DGLA (provided exogenously) inhibited the formation of leukotriene B4, (LTB4) and 20-hydroxy-leukotriene B4 (20-OH-LTB4). The IC50 for 15-HETre inhibition of both LTR, and 20-OH-LTB4 in A23187-stimulated neutrophils was 5 microM. This inhibition could be reversed by removing the compounds from the cells. Taken together, these data reveal that 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.
Chilton-Lopez
Department of Internal Medicine, Bowman Gray School of Medicine, Winston-Salem, NC 27157, USA.
Surette
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ME
Swan
D D
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Fonteh
A N
AN
Johnson
M M
MM
Chilton
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D015126:8,11,14-Eicosatrienoic Acid / Q000097:blood / Q000378:metabolism; D000328:Adult; D016718:Arachidonic Acid / Q000097:blood / Q000378:metabolism; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000097:blood; D007975:Leukotriene B4 / Q000097:blood / Q000378:metabolism; D008875:Middle Aged; D018375:Neutrophil Activation; D009504:Neutrophils / Q000201:enzymology / Q000378:metabolism*; D017965:gamma-Linolenic Acid / Q000097:blood / Q000378:metabolism*
D006893:Hydroxyeicosatetraenoic Acids; D007975:Leukotriene B4; D016718:Arachidonic Acid; C025984:15-hydroxy-5,8,11,13-eicosatetraenoic acid; D017965:gamma-Linolenic Acid; D015126:8,11,14-Eicosatrienoic Acid