ω-3 Fatty acids suppress monocyte adhesion to human endothelial cells: role of endothelial PAF generation

Abstract

Monocyte-endothelium interaction is a fundamental process in many acute and chronic inflammatory diseases. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are fish oil-derived alternative (ω-3) precursor fatty acids implicated in the suppression of inflammatory events. We investigated their influence on rolling and adhesion of monocytes to human umbilical vein endothelial cells (HUVEC) under laminar flow conditions in vitro. Exposure of HUVEC to tumor necrosis factor (TNF-α) strongly increased 1) surface expression of intercellular adhesion molecule (ICAM-1), vascular cell adhesion molecule (VCAM-1), and E-selectin, 2) platelet-activating factor (PAF) synthesis as assessed by thrombin challenge, and 3) rate of rolling and adhesion of monocytes. Preincubation of HUVEC with EPA or DHA markedly suppressed PAF synthesis, monocyte rolling, and adherence, whereas expression of endothelial adhesion molecules was unchanged. Also, PAF receptor antagonists markedly suppressed the adhesion rate of monocytes, and EPA or DHA revealed no additional inhibitory capacity. In contrast, arachidonic acid partially reversed the effect of the antagonist. We conclude that ω-3 fatty acids suppress rolling and adherence of monocytes on activated endothelial cells in vitro by affecting endothelial PAF generation.

Short-Time Infusion of Fish Oil-Based Lipid Emulsions, Approved for Parenteral Nutrition, Reduces Monocyte Proinflammatory Cytokine Generation and Adhesive Interaction with Endothelium in Humans

“…Recent studies from our group using -3 fatty acid-incubated endothelial cells showed rapid incorporation of EPA and DHA into the sn-2 position of phosphatidylcholine, phosphatidylethanolamine, and phosphatidylinositol pool including its PAF precursor subclasses. Moreover, decreased PAF formation was noted under these conditions (30,31). In addition, at the transcriptional level, the NFB has been described as activated by arachidonic acid, but not by EPA (32), and DHA was reported to prevent TNF-␣-mediated activation of NFB (10).…”

Omega 3 (n−3) fatty acids down-regulate nuclear factor-kappa B (NF-κB) gene and blood cell adhesion molecule expression in patients with homozygous sickle cell disease

“…Therefore, therapeutic approaches to reduce expression of CD62L and CD11B have been important strategies to prevent vaso-occlusion in sickle cell disease [50]. In vitro [56,57] and in vivo [13] studies in conditions other than SCD have revealed that supplementation with n−3 resulted in significant reduction in blood cell adhesive molecules. Interestingly, we observed a significant reduction of adhesive molecules in monocytes in the group supplemented with n−3 fatty acids, the finding which denotes improvement in SCD-associated chronic inflammatory state.…”

Differences in Serum Phospholipid Fatty Acid Compositions and Estimated Desaturase Activities between Japanese Men with and without Metabolic Syndrome

“…As the percentage of C20:4n-6 did not differ between subjects with and without MetS, we consider phospholipase A2 activity, which generates platelet activating factor (PAF) and PAF-like phospholipids with release of C20:4n-6, to have been accelerated. PAF-like phospholipids are recognized in the atherogenic lipoproteins of small, dense LDL [38][39][40][41] . Zak et al reported that the severity of MetS was associated with the progression of oxidative stress, as evaluated with conjugated dienes in LDL 28) .…”