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Type: Journal article
Title: n-6 and n-3 polyunsaturated fatty acids stimulate translocation of protein kinase C a, bI, bII and e and enhance agonist-induced NADPH oxidase in macrophages
Author: Huang, Z.
Hii, C.
Rathjen, D.
Poulos, A.
Murray, A.
Ferrante, A.
Citation: Biochemical Journal, 1997; 325(2):553-557
Issue Date: 1997
ISSN: 0264-6021
Statement of
Zhi Hua Huang, Charles S. T. Hii, Deborah A. Rathjen, Alf Poulos, Andrew W. Murray and Antonio Ferrante
Abstract: The polyunsaturated fatty acids (PUFA), arachidonic acid (AA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were poor inducers of oxygen-dependent respiratory activity (chemiluminescence) in human monocytes and macrophages, but markedly enhanced the response to the tripeptide, N-formylmethionyl-leucyl-phenylalanine. The effects of these fatty acids were seen at concentrations of 1 µg/ml. A similar enhancement was seen with PMA, a stimulus that acts on protein kinase C (PKC), or calcium ionophore (A23187), which increases intracellular calcium, suggesting that the effect of the fatty acids was post-surface receptor binding. HL-60 cells, differentiated to macrophage-like cells by culture in the presence of vitamin D3, were similarly affected by the fatty acids. In experiments in which the time of pre-exposure of the monocytes to PUFA was varied, it was found that the priming effect induced by AA, EPA and DHA was maximal at 5 min. The ability of these fatty acids to synergize with other agonists was completely lost if the fatty acids were either methylated or oxidized to the hydro and hydroperoxy derivatives. Saturated fatty acids were inactive. Western blot analysis demonstrated that the PUFA induced the translocation of PKCa, -bI, -bII and -e isoenzymes to a particulate fraction. The synergistic response between fatty acids and A23187 was completely inhibited by pretreating the cells with a PKC inhibitor, GF-109203X, or by pretreatment of monocytes with PMA for 18 h, to deplete PKC levels. From these investigations it is evident that PUFA prime macrophages, causing increased/synergistic oxidative respiratory burst activity to other stimuli and that this priming is dependent on PKC translocation and activation.
Keywords: PUFA, polyunsaturated fatty acids
AA, arachidonic acid
EPA, eicosapentaenoic acid
DHA, docosahexaenoic acid
fMLP, N-formylmethionyl-leucyl-phenylalanine
PKC, protein kinase C
DPC, dipalmitoylphosphatidylcholine
Rights: The Biochemical Society, London © 1997
DOI: 10.1042/bj3250553
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