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Type: Journal article
Title: Neutrophil oxygen radical generation. Synergistic responses to tumor necrosis factor and mono/polyunsaturated fatty acids
Author: Li, Y.
Ferrante, A.
Poulos, A.
Harvey, D.
Citation: Journal of Clinical Investigation, 1996; 97(7):1605-1609
Issue Date: 1996
ISSN: 0021-9738
Abstract: In inflammatory reactions there are complex interactions of protein mediators (cytokines) and mediators derived from lipids. An important event in inflammation is superoxide production, in relation to microbicidal activity as well as tissue damage. We have studied interactions of lipid mediators with a cytokine mediator tumor necrosis factor alpha (TNF) in stimulating superoxide production by human neutrophils for this reason and because it throws light on intracellular signals activating this response. Pretreatment of neutrophils with TNF markedly augmented the amount of superoxide produced in response to AA but not to either a 20 carbon saturated fatty acid, or the hydroxy- or hydroperoxy-derivatives of AA. Not only were other polyunsaturated fatty acids (eicosapentanoic, docosahexaenoic, linolenic, linoleic acid) as effective as AA but so was the monounsaturated fatty acid, oleic acid. Indeed TNF primed the neutrophils for an increased response to a major mediator of inflammation, leukotriene B4, which is a product of AA metabolism via the lipoxygenase pathway. The data demonstrate that two major types of mediators generated during an inflammatory response have synergistic action on neutrophils in the generation of reactive oxygen species. In contrast, neutrophils primed with TNF and challenged with PGE2, a product of AA metabolism via the cyclooxygenase pathway, showed a reduced chemiluminescence response. This identifies an important interaction between unsaturated lipids and cytokines which is likely to play a critical role in disease processes and nutrient modulation of the immune responses.
Keywords: Neutrophils
Reactive Oxygen Species
Fatty Acids, Unsaturated
Arachidonic Acid
Leukotriene B4
Tumor Necrosis Factor-alpha
Recombinant Proteins
Luminescent Measurements
Drug Synergism
In Vitro Techniques
DOI: 10.1172/JCI118585
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Appears in Collections:Aurora harvest 5
Paediatrics publications

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