The Mechanism of Inhibitory Effect of Eicosapentaenoic Acid on Phagocytic Activity and Chemotaxis of Human Neutrophil Granulocytes

Sipka, Sándor; Dey, Indranil; Buda, Csaba; Csongor, J.; Szegedi, Gyula; Farkas, Tibor

doi:10.1006/clin.1996.0072

Cited by 21 publications

(11 citation statements)

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“…Both agents, as reported previously (13,15), also inhibited the FMLP-activated generation of reactive oxidants by these cells and were particularly effective in neutralizing the Ca 2ϩ -dependent, prooxidative interactions of pneumolysin with neutrophils, which are secondary to the pore-forming actions of the toxin (4). Although the exact molecular and biophysical mechanisms by which DHA and EPA enable the neutrophil plasma membrane to resist pneumolysin remain to be established, effects on membrane fluidity and stability are likely to be involved (6,8,15). This contention is supported by the observation that DHA-mediated resistance of neutrophils to the toxin was essentially unaffected by washing of the cells.…”

Section: Pneumolysin (418 Ng/ml)-mediated Influx Of Casupporting

confidence: 58%

Docosahexaenoic Acid and Eicosapentaenoic Acid Antagonize the Proinflammatory Interactions of Pneumolysin with Human Neutrophils

et al. 2004

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Pneumolysin (4.18 ng/ml)-mediated influx of Ca2؉ and augmentation of the chemoattractant-activated generation of reactive oxidants was antagonized by pretreatment of human neutrophils with the omega-3 polyunsaturated fatty acids docosahexaenoic acid and eicosapentaenoic acid (1.25 to 5 g/ml). These agents may have potential in attenuating the proinflammatory properties of this pneumococcal toxin.Notwithstanding complement-activating properties, poreforming interactions with neutrophils and monocytes, resulting in influx of Ca 2ϩ , have been implicated in the proinflammatory activities of the pneumococcal toxin, pneumolysin (1,2,3,4,11). Rather than contributing to the eradication of the infection, however, the resultant, predominantly neutrophil-mediated inflammatory response appears to favor persistence and extrapulmonary dissemination of the pneumococcus (7, 9).Although no pharmacological antagonists of pneumolysin have, to our knowledge, been described, we reasoned that agents, such as the omega-3 polyunsaturated fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), which increase neutrophil membrane fluidity and stability may interfere with the proinflammatory, pore-forming activities of the toxin. The present study was designed to investigate the potential of DHA and EPA to neutralize two related proinflammatory activities of pneumolysin, these being the toxinmediated influx of Ca 2ϩ into human neutrophils and Ca 2ϩ -dependent sensitization of these cells for increased production of toxic reactive oxidants (4).Endotoxin-free (Ͻ2 pg/ml) recombinant pneumolysin (specific activity, 4 ϫ 10 6 hemolytic units/mg) was expressed in Escherichia coli and purified from cell extracts as previously described (12).Neutrophils were isolated from heparinized (5 U of preservative-free heparin/ml) venous blood of healthy, adult human volunteers (4) and resuspended to 10 7 neutrophils/ml in phosphate-buffered saline (0.15 M, pH 7.4).cis 7,10,13,16,8,11,14,17-EPA were purchased from Sigma Chemical Co. (St. Louis, Mo.) and made to stock concentrations of 25 mg/ml in ethanol. Dilutions were made in ethanol, and these agents were used at final concentrations of 1.25, 2.5, and 5 g/ml in a final ethanol concentration of 0.1%. All control systems included in the experiments described below contained 0.1% ethanol, which did not interfere with the biological activity of pneumolysin.Fura-2/AM (Sigma) was used as the fluorescent Ca 2ϩ -sensitive indicator to measure alterations in neutrophil cytosolic Ca 2ϩ as previously described (4). The neutrophils were preloaded with fura-2/AM (final concentration, 2 M) for 30 min at 37°C in phosphate-buffered saline, washed, and resuspended in Hanks balanced salt solution (pH 7.4, 1.25 mM CaCl 2 ; Highveld Biological Pty. Ltd., Johannesburg, South Africa). The cells (1 ϫ 10 6 /ml) were then preincubated for 10 min at 37°C with or without DHA or EPA (1.25 to 5 g/ml) and transferred thereafter to cuvettes, maintained at 37°C in a Hitachi 650 10S fluorescence spectrophotometer with e...

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Section: Pneumolysin (418 Ng/ml)-mediated Influx Of Casupporting

confidence: 58%

Docosahexaenoic Acid and Eicosapentaenoic Acid Antagonize the Proinflammatory Interactions of Pneumolysin with Human Neutrophils

et al. 2004

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“…A known antiinflammatory fatty acid, eicosapentaenoic acid, was found to increase membrane fluidity in resting polymorphonuclear membrane cells, but decreased membrane fluidity in activated polymorphonuclear membrane cells, and thus decreased their chemotaxis and phagocytosis. 42 In a canine myocardial reperfusion injury model, treatment with Fluosol, a P-188-containing agent, decreased neutrophil infiltration and chemotaxis, but it only decreased lysozyme production 1 hour after reperfusion. 3 Indirect correlation of decreased chemotaxis to increased membrane rigidity has been shown in an examination of lazy leukocyte syndrome.…”

Section: Discussionmentioning

confidence: 98%

Surfactant poloxamer 188—related decreases in inflammation and tissue damage after experimental brain injury in rats

Curry¹,

Wright²,

Lee³

et al. 2004

Journal of Neurosurgery: Pediatrics

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“…The n-3 long chain PUFAs (such as EPA) modulate immune responses in a wide variety of in vivo and in vitro studies in numerous organisms reviewed by [74]–[76]. PUFAs (such as EPA) can affect numerous aspects of the host immune response, which would directly benefit plastid function in E. chlorotica including components of the innate immune response such as inflammation [77], superoxide production [78], phagocytosis [79], and peroxide production [80]. High amounts of such PUFAs have a negative effect on the ability of hosts to clear pathogen infection [75], [81]–[86].…”

Section: Discussionmentioning

confidence: 99%

Lipid Accumulation during the Establishment of Kleptoplasty in Elysia chlorotica

Pelletreau

Weber

et al. 2014

PLoS ONE

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The establishment of kleptoplasty (retention of “stolen plastids”) in the digestive tissue of the sacoglossan Elysia chlorotica Gould was investigated using transmission electron microscopy. Cellular processes occurring during the initial exposure to plastids were observed in laboratory raised animals ranging from 1–14 days post metamorphosis (dpm). These observations revealed an abundance of lipid droplets (LDs) correlating to plastid abundance. Starvation of animals resulted in LD and plastid decay in animals <5 dpm that had not yet achieved permanent kleptoplasty. Animals allowed to feed on algal prey (Vaucheria litorea C. Agardh) for 7 d or greater retained stable plastids resistant to cellular breakdown. Lipid analysis of algal and animal samples supports that these accumulating LDs may be of plastid origin, as the often algal-derived 20∶5 eicosapentaenoic acid was found in high abundance in the animal tissue. Subsequent culturing of animals in dark conditions revealed a reduced ability to establish permanent kleptoplasty in the absence of photosynthetic processes, coupled with increased mortality. Together, these data support an important role of photosynthetic lipid production in establishing and stabilizing this unique animal kleptoplasty.

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The Mechanism of Inhibitory Effect of Eicosapentaenoic Acid on Phagocytic Activity and Chemotaxis of Human Neutrophil Granulocytes

Cited by 21 publications

References 0 publications

Docosahexaenoic Acid and Eicosapentaenoic Acid Antagonize the Proinflammatory Interactions of Pneumolysin with Human Neutrophils

Docosahexaenoic Acid and Eicosapentaenoic Acid Antagonize the Proinflammatory Interactions of Pneumolysin with Human Neutrophils

Surfactant poloxamer 188—related decreases in inflammation and tissue damage after experimental brain injury in rats

Lipid Accumulation during the Establishment of Kleptoplasty in Elysia chlorotica

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