N-3 vs. n-6 fatty acids differentially influence calcium signalling and 
adhesion of inflammatory activated monocytes: impact of lipid rafts

Schaefer, Martina Barbara; Schaefer, Christian Alexander; Schifferings, Stefanie; Kuhlmann, Christoph Ruediger Wolfram; Urban, Annett; Benscheid, Utz; Fischer, Tobias; Hecker, Matthias; Morty, Rory E.; Vadasz, Istvan; Herold, Susanne; Witzenrath, Martin; Seeger, Werner; Erdogan, Ali; Mayer, Konstantin

doi:10.1007/s00011-016-0971-9

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N-3 vs. n-6 fatty acids differentially influence calcium signalling and adhesion of inflammatory activated monocytes: impact of lipid rafts

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Morty, Rory E.
Lung Development and Remodeling, Max Planck Institute for Heart and Lung Research, Max Planck Society;

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Seeger, Werner
Lung Development and Remodeling, Max Planck Institute for Heart and Lung Research, Max Planck Society;

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Citation

Schaefer, M. B., Schaefer, C. A., Schifferings, S., Kuhlmann, C. R. W., Urban, A., Benscheid, U., et al. (2016). N-3 vs. n-6 fatty acids differentially influence calcium signalling and adhesion of inflammatory activated monocytes: impact of lipid rafts. INFLAMMATION RESEARCH, 65(11), 881-894. doi:10.1007/s00011-016-0971-9.

Cite as: https://hdl.handle.net/21.11116/0000-0001-BD5F-1

Abstract

Anti-inflammatory n-3 fatty acids (FA) like docosahexaenoic acid (DHA) opposed to the pro-inflammatory n-6 FA arachidonic acid (AA) might modulate lipid rafts within the cell membrane by differential incorporation. In inflammation, monocyte adhesion to endothelial cells is a crucial step mediated by intracellular calcium changes. We investigated whether lipid rafts mediate FA-induced modulation of adhesion and intracellular calcium. In isolated human monocytes and monocytic U937 cells we measured adhesion to human umbilical vein endothelial cells (HUVEC) using a parallel flow chamber and a static assay, adhesion molecules by FACScan, and intracellular calcium by fluorescence. Monocyte lipid rafts were isolated by ultracentrifugation and submitted to gas chromatography for FA analysis. Pre-incubation with AA or DHA resulted in a predominant incorporation of the respective FA into raft compared to non-raft fraction. DHA as compared to AA significantly reduced monocyte adhesion and calcium release after stimulation with TNF-alpha while expression of adhesion molecules remained unchanged. Pre-treatment with a calcium chelator abolished the effect of FA on calcium and adhesion. Disruption of lipid rafts prevented FA-induced modulations. Incorporation of FA into lipid rafts seem to be crucial for modulation of adhesion under inflammatory conditions.