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

• Published in: Inflammation research 2016-11, Vol.65 (11), p.881-894
• Main Authors: Schaefer, Martina Barbara, Schaefer, Christian Alexander, Schifferings, Stefanie, Kuhlmann, Christoph Rüdiger Wolfram, Urban, Annett, Benscheid, Utz, Fischer, Tobias, Hecker, Matthias, Morty, Rory E., Vadasz, Istvan, Herold, Susanne, Witzenrath, Martin, Seeger, Werner, Erdogan, Ali, Mayer, Konstantin
• Format: Article
• Language: English
• Subjects: Allergology; Antigens, CD - metabolism; Arachidonic Acid - pharmacology; Biomedical and Life Sciences; Biomedicine; Calcium Signaling - drug effects; Cell Adhesion - drug effects; Cells, Cultured; Dermatology; Docosahexaenoic Acids - pharmacology; Human Umbilical Vein Endothelial Cells - drug effects; Human Umbilical Vein Endothelial Cells - metabolism; Human Umbilical Vein Endothelial Cells - physiology; Humans; Immunology; Membrane Microdomains - drug effects; Membrane Microdomains - metabolism; Monocytes - drug effects; Monocytes - metabolism; Monocytes - physiology; Neurology; Original Research Paper; Pharmacology/Toxicology; Rheumatology; Tumor Necrosis Factor-alpha - pharmacology; U937 Cells
• ISSN: 1023-3830; 1420-908X
• DOI: 10.1007/s00011-016-0971-9

Background 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. Methods 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. Results 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-α 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. Conclusion Incorporation of FA into lipid rafts seem to be crucial for modulation of adhesion under inflammatory conditions.