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Inflamm Res. 2016 Nov;65(11):881-894. Epub 2016 Jul 6.

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

Author information

1
University of Giessen Lung Center (UGLC), University Hospital of Giessen and Marburg, Klinikstr. 33, 35392, Giessen, Germany.
2
Department of Internal Medicine II, University Hospital of Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany.
3
Department of Internal Medicine I, University Hospital of Giessen and Marburg, Klinikstr. 33, 35392, Giessen, Germany.
4
International Neuroscience Institute, INI Hannover GmbH, Rudolf Pichlmayr Str. 4, 30625, Hannover, Germany.
5
Department of Anaesthesiology, University of Düsseldorf, Moorenstr. 5, 40225, Düsseldorf, Germany.
6
German Cancer Research Center, Im Neuenheimer Feld 280, 69120, Heidelberg, Germany.
7
Department of Anaesthesiology, University Hospital of Giessen and Marburg, Giessen, Germany.
8
Department of Lung Development and Remodelling, Max-Planck-Institute, Parkstr. 1, 61231, Bad Nauheim, Germany.
9
Department of Pneumology, Charité, University of Berlin, Chariteplatz 1, 10117, Berlin, Germany.
10
University of Giessen Lung Center (UGLC), University Hospital of Giessen and Marburg, Klinikstr. 33, 35392, Giessen, Germany. Konstantin.Mayer@innere.med.uni-giessen.de.

Abstract

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.

KEYWORDS:

Adhesion; Calcium; Fatty acids; Inflammation; Lipid rafts

PMID:
27384606
DOI:
10.1007/s00011-016-0971-9
[Indexed for MEDLINE]

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