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Journal of Lipid Research, Vol 37, 1234-1245, Copyright © 1996 by Lipid Research, Inc.
BS Robinson, CS Hii, A Poulos and A Ferrante
Although tumor necrosis factor-alpha (TNF-alpha) has been shown to induce
marked changes in the physiology/pathophysiology of cells, little is known
about the effects of this cytokine on cellular lipid metabolism. In this
study we examined the effects of TNF-alpha on the metabolism of
eicosatetraenoic acid (arachidonic acid, (20:4(n-6)) in human neutrophils.
Pretreatment of neutrophils with TNF-alpha caused a rapid increase in the
incorporation of [1-14C]20:4(n-6) substrate into cellular
phosphatidylinositol and phosphatidic acid and a slower rise in the
incorporation into phosphatidylcholine and phosphatidylethanolamine.
Radioactivity was exclusively associated with the sn-2 position of each
molecule. The labeling pattern of other phospholipids, neutral lipids, and
eicosanoids was unchanged. TNF-alpha had no effect on the distribution of
radioactivity in 1-acyl, 1-alkyl, and 1-alk-1-enyl subclasses of
phosphatidylcholine, phosphatidylethanolamine, and triglyceride. Chain
elongation, beta- oxidation and desaturation of [1-14C]20:4(n-6) were not
modulated by the cytokine. TNF-alpha stimulated the release of
[3H]20:4(n-6) from prelabeled neutrophils and also induced the production
of endogenous unesterified 20:4(n-6). Concomitantly, treatment with the
cytokine caused a decrease in the mass of cellular phosphatidylinositol,
phosphatidylcholine, and phosphatidylethanolamine and an increase in the
levels of corresponding lysophospholipids, but had no significant effect on
sphingomyelin, phosphatidic acid, diglyceride, and other lipids. TNF-alpha
did not evoke neutrophils prelabeled with [3H]lyso platelet activating
factor to produce [3H]phosphatidylethanol, [3H]phosphatidic acid, or
[3H]diglyceride in the presence of ethanol, indicating that phospholipases
D and C were not activated. Treatment of the leukocytes with the cytokine
had no effect on the activity of neutral and acidic sphingomyelinase. These
data collectively provide evidence that TNF-alpha specifically induces the
turnover of neutrophil phosphatidylinositol, phosphatidylcholine and
phosphatidylethanolamine, which are enriched with 20:4(n-6) by the
activation of phospholipase A2.
ARTICLES
Effect of tumor necrosis factor-alpha on the metabolism of arachidonic acid in human neutrophils
Department of Immunology, Women's and Children's Hospital, North Adelaide, Australia.
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