Phytohaemagglutinin stimulation of human lymphocytes Effect of fatty acids on uridine uptake and phosphogylceride fatty acid profile

Weyman, Christine; Morgan, Sheila J.; Belin, J; Smith, Anthony D.

doi:10.1016/0304-4165(77)90123-4

Cited by 65 publications

(20 citation statements)

References 21 publications

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“…The ability of lymphocytes to incorporate and use exogenously derived free fatty acids has been reported by numerous workers, as has enhanced fatty acid uptake after mitogen activation (5,(31)(32)(33) (35,36). This level is equivalent to the amount of distearoylphosphatidylcholine observed in the stearic acid-treated T cells.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Absence of unsaturated fatty acid synthesis in murine T lymphocytes.

Buttke

Cleave

Steelman

et al. 1989

Proc. Natl. Acad. Sci. U.S.A.

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Stearic acid is toxic for T lymphocytes in vitro but has little effect on B lymphocytes. To investigate the molecular basis for this difference, purified murine T and B lymphocytes were compared for their abilities to incorporate and metabolize stearic acid. Unstimulated T and B cells incorporated identical amounts of stearic acid into six different phospholipids and four neutral lipids. After mitogen stimulation, fatty acid uptake was increased in both lymphocyte types, but cell-specific differences were seen in the distribution of stearic acid among the various cellular lipids. Doses of stearic acid that selectively inhibited T-cell proliferation resulted in a 5-fold greater accumulation of distearoylphosphatidylcholine in T cells than in B cells. Whereas T cells did not desaturate the exogenously derived stearic acid, up to 25% of the saturated fatty acid was converted to oleic acid in B cells. These findings suggested a deficiency of stearoyl-CoA desaturase (acyl-CoA, hydrogen-donor:oxygen oxidoreductase, EC 1.14.99.5) activity in T cells, which was confirmed by subsequent studies. Cell-free extracts from B cells displayed nearly 20-fold more stearoylCoA desaturase activity than T-cell extracts, and the level of stearoyl-CoA desaturase mRNA was 30-fold higher in B cells. Collectively, our data indicate that murine T cells are deficient in unsaturated fatty acid synthesis. The deficiency of stearoylCoA desaturase in T cells may represent the basis for the differing sensitivities of T and B lymphocytes to inhibition by saturated fatty acids.Saturated and unsaturated fatty acids markedly affect lymphocyte function both in vivo and in vitro (for review, see refs. 1-3). In general, saturated fatty acids and high levels (>20 AuM) of unsaturated fatty acids are inhibitory, whereas low amounts (<10 ,M) of unsaturated fatty acids enhance lymphocyte growth and function (4-8). The mechanisms by which fatty acids alter lymphocyte function are not fully understood. Polyunsaturated fatty acids are converted to various icosanoids having potent immunopharmacological properties (9, 10). By contrast saturated and monounsaturated fatty acids have been proposed to act by changing the organization or physical properties of immune cell membranes, although this remains controversial (3, 10, 11).In studies carried out in vivo (3, 12, 13) and in vitro (8, 14), fatty acids have been shown to have a greater effect on T cells and cell-mediated immunity than on B cells and humoral immunity. For example, using highly purified murine T and B lymphocytes, we showed that stearic acid potently inhibited T-cell proliferation but had much less effect on B-cell proliferation (8). At the same concentration (50AM), oleic acid was without effect; however, when added simultaneously with stearic acid, oleic acid could obviate the inhibitory effects of the saturated fatty acid (8,15 For analysis of molecular species, radiolabeled phosphatidylcholine fractions were converted to diacylglycerides by phospholipase C digestion (19) followed by ben...

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Section: Discussionmentioning

confidence: 99%

“…[1][2][3]. In general, saturated fatty acids and high levels (>20 AuM) of unsaturated fatty acids are inhibitory, whereas low amounts (<10 ,M) of unsaturated fatty acids enhance lymphocyte growth and function (4)(5)(6)(7)(8). The mechanisms by which fatty acids alter lymphocyte function are not fully understood.…”

mentioning

confidence: 99%

Absence of unsaturated fatty acid synthesis in murine T lymphocytes.

Buttke

Cleave

Steelman

et al. 1989

Proc. Natl. Acad. Sci. U.S.A.

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“…Therefore, it can be speculated that the AA thus liberated is taken up by bystander cells to be metabolized to eicosanoids, representing a particular transcellular pathway for AA metabolism. In addition, it has been shown that AA affects leukocyte adhesion by suppressing the expression of adhesion molecules on endothelial cells (45)(46)(47), activates NADPH oxidase (48 -50), and exerts direct effects on phagocyte H ϩ and Ca 2ϩ ion flux (51)(52)(53)(54). These actions may contribute to propagation of inflammatory processes, and the secreted AA-S100A8/A9 complex may here be involved, probably as the shuttle protein to reach target cells.…”

Section: Discussionmentioning

confidence: 99%

The Two Calcium-binding Proteins, S100A8 and S100A9, Are Involved in the Metabolism of Arachidonic acid in Human Neutrophils

Kerkhoff¹,

Klempt²,

Kaever³

et al. 1999

Journal of Biological Chemistry

154

160

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Recently, we identified the two myeloid related protein-8 (MRP8) (S100A8) and MRP14 (S100A9) as fatty acid-binding proteins (Klempt, M., Melkonyan, H., Nacken, W., Wiesmann, D., Holtkemper, U., and Sorg, C. (1997) FEBS Lett. 408, 81-84). Here we present data that the S100A8/A9 protein complex represents the exclusive arachidonic acid-binding proteins in human neutrophils. Binding and competition studies revealed evidence that (i) fatty acid binding was dependent on the calcium concentration; (ii) fatty acid binding was specific for the protein complex formed by S100A8 and S100A9, whereas the individual components were unable to bind fatty acids; (iii) exclusively polyunsaturated fatty acids were bound by S100A8/A9, whereas saturated (palmitic acid, stearic acid) and monounsaturated fatty acids (oleic acid) as well as arachidonic acid-derived eicosanoids (15-hydroxyeicosatetraenoic acid, prostaglandin E 2 , thromboxane B 2 , leukotriene B 4 ) were poor competitors. Stimulation of neutrophil-like HL-60 cells with phorbol 12-myristate 13-acetate led to the secretion of S100A8/A9 protein complex, which carried the released arachidonic acid. When elevation of intracellular calcium level was induced by A23187, release of arachidonic acid occurred without secretion of S100A8/A9. In view of the unusual abundance in neutrophilic cytosol (approximately 40% of cytosolic protein) our findings assign an important role for S100A8/A9 as mediator between calcium signaling and arachidonic acid effects. Further investigations have to explore the exact function of the S100A8/A9-arachidonic acid complex both inside and outside of neutrophils.The two myeloid-related proteins, MRP8 and MRP14, belong to the S100 family of calcium-binding proteins (for review, see Refs. 1-4). They are composed of two distinct EF-hands flanked by hydrophobic regions at either terminus and separated by a central hinge region, and they form a heterodimeric complex in a Ca 2ϩ -dependent manner. Heizmann and Schä fer (5) proposed a new logical nomenclature for these genes based on the physical arrangement of the genes encoding the S100 family on chromosome 1q21. According to this nomenclature, MRP8 and MRP14 are referred to as S100A8 and S100A9, respectively.Both proteins are expressed in circulating neutrophils and monocytes but are absent in normal tissue macrophages and lymphocytes (6 -9). Under chronic inflammatory conditions, such as psoriasis and malignant disorders, they are also expressed in the epidermis (10 -12). S100A8 and S100A9 are predominantly localized in the cytoplasm. Upon elevation of the intracellular calcium level they are translocated from the cytosol to cytoskeleton and to plasma membrane (13). At a later time point, they appear as noncovalently associated S100A8/A9 heterodimers on the surface of monocytes (14). The mechanism by which the S100A8/A9 heterodimer penetrates the plasma membrane and how the S100A8/A9 protein complex is anchored into the cell membrane, remains unclear since both proteins lack a transmembrane region. Upon th...

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“…Anel et al [17] reported the fatty acid composition of the total lipid fraction of freshly prepared human peripheral blood lymphocytes, and the fatty acid composition of phospholipids and phospholipid classes has been reported for human PBL [17,31] and animal lymphocytes from many sources [e.g. 6,8].…”

Section: C3lmentioning

confidence: 99%

Incorporation of fatty acids by concanavalin A-stimulated lymphocytes and the effect on fatty acid composition and membrane fluidity

Calder

Yaqoob

Harvey

et al. 1994

Biochemical Journal

208

144

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The fatty acid compositions of the neutral lipid and phospholipid fractions of rat lymph node lymphocytes were characterized. Stimulation of rat lymphocytes with the T-cell mitogen concanavalin A resulted in significant changes in the fatty acid composition of both neutral lipids and phospholipids (a decrease in the proportions of stearic, linoleic and arachidonic acids and an increase in the proportion of oleic acid). Membrane fluidity was measured using nitroxide spin-label e.s.r., and increased during culture with concanavalin A. Culturing the lymphocytes in the absence of mitogen did not affect fatty acid composition or membrane fluidity. The uptake and fate of palmitic, oleic, linoleic and arachidonic acids were studied in detail; there was a timedependent incorporation of each fatty acid into all lipid classes but each fatty acid had a characteristic fate. Palmitic and arachidonic acids were incorporated principally into phospholipids whereas oleic and linoleic acids were incorporated in similar proportions into phospholipids and triacylglycerols. Oleic acid was incorporated mainly into phosphatidylcholine, palmitic and linoleic acids were incorporated equally into phosphatidylcholine and phosphatidylethanolamine, and arachidonic acid was incorporated mainly into phosphatidylethanolamine. Supplementation of the culture medium with particular fatty acids (myristic, palmitic, stearic, oleic, linoleic, a-linolenic, arachi-

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Phytohaemagglutinin stimulation of human lymphocytes Effect of fatty acids on uridine uptake and phosphogylceride fatty acid profile

Cited by 65 publications

References 21 publications

Absence of unsaturated fatty acid synthesis in murine T lymphocytes.

Absence of unsaturated fatty acid synthesis in murine T lymphocytes.

The Two Calcium-binding Proteins, S100A8 and S100A9, Are Involved in the Metabolism of Arachidonic acid in Human Neutrophils

Incorporation of fatty acids by concanavalin A-stimulated lymphocytes and the effect on fatty acid composition and membrane fluidity

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