Nutritional lipid emulsions modulate cellular signaling and activation of human neutrophils.
Although numerous studies suggest that nutritional lipids modulate human immune responses, the mechanism behind this observation remains unclear. On the basis of the hypothesis that lipids might affect cellular signaling we evaluated the effects of various lipid emulsions on two major pathways involved in neutrophil activation: second messenger (Ca(2)+) mobilization and protein kinase C (PKC) activation. Activation by opsonized yeast particles (serum-treated zymosan; STZ) increased cytosolic [Ca(2)+] ([Ca(2)+](i)) in neutrophils, with an initial slow rise that turned into a fast phase until a plateau was reached. The PKC activator 4-alpha-phorbol 12-myristate 13-acetate (PMA) markedly increased the initial STZ-induced [Ca(2)+](i) rise. This PMA effect was mimicked by emulsions containing medium-chain triglycerides (MT), but not by long-chain triglycerides (LT) or structured lipids (SL). However, like PMA, all emulsions decreased the STZ-induced [Ca(2)+](i) plateau and all activated purified PKC, suggesting that only MT emulsions activate PKC in the context of the intact cell. MT, like PMA, evoked a leftward shift of the dose-response curve for the STZ-induced [Ca(2)+](i) rise, indicating PKC-dependent sensitization of neutrophils for stimulation by STZ. This study is the first to show that nutritional lipids distinctively modulate cellular signaling and stimulation of neutrophils through effects on calcium mobilization and PKC activation: i) MT emulsions sensitize neutrophils for STZ in a PKC-dependent manner, and ii) MT, LT, and SL emulsions all reduce the stimulatory effect of STZ in a nonspecific manner. -- Wanten, G., S. van Emst-de Vries, T. Naber, and P. Willems. Nutritional lipid emulsions modulate cellular signaling and activation of human neutrophils. J. Lipid Res. 2001. 42: 428--436.
Department of Gastroenterology and Hepatology, University Medical Center, 6525 GA Nijmegen, The Netherlands.
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Wanten
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van Emst-De Vries
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Naber
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Willems
D001769:Blood; D002118:Calcium / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004655:Emulsions; D004963:Estrenes / Q000494:pharmacology; D005456:Fluorescent Dyes; D016257:Fura-2 / Q000031:analogs & derivatives; D006801:Humans; D008055:Lipids / Q000494:pharmacology*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D018375:Neutrophil Activation / Q000187:drug effects*; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D011760:Pyrrolidinones / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects*; D013050:Spectrometry, Fluorescence; D019311:Staurosporine / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors; D015054:Zymosan / Q000494:pharmacology
D004655:Emulsions; D004963:Estrenes; D005456:Fluorescent Dyes; D008055:Lipids; D010726:Phosphodiesterase Inhibitors; D011760:Pyrrolidinones; C049925:fura-2-am; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D009240:N-Formylmethionine Leucyl-Phenylalanine; D015054:Zymosan; D011493:Protein Kinase C; D010738:Type C Phospholipases; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium; D016257:Fura-2