Docosahexaenoic and Eicosapentaenoic Acids Inhibit in Vitro Human Lymphocyte-Endothelial Cell Adhesion

Abstract

Dietary supplementation with fish oil, which contains high amounts of long chain omega 3 ((n-3)) polyunsaturated fatty acids (PUFAs), particularly docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), has recently been shown to have protective and ameliorative effects on diseases characterized by chronic inflammatory reactions. Interactions between vascular endothelium, mononuclear cells, and cytokines are crucial steps in the course of inflammatory processes such as chronic graft rejection. We therefore studied the effects of DHA and EPA on both the adhesion of peripheral blood lymphocytes (PBL) to human endothelial cells (EC) in culture and the expression of EC-adhesion molecules and their counterreceptors on PBL. The addition of DHA or EPA to the adhesion assay significantly decreased the adhesion of PBL to untreated EC and tumor necrosis factor-alpha (TNF alpha)-, interleukin (IL) 4-, and lipopolysaccharide-stimulated EC. When EC were pretreated with (n-3) PUFAs for 18 hr, washed, and then stimulated by TNF alpha, IL-4, or lipopolysaccharide, PBL adhesion was also significantly reduced compared with controls. We also showed that PBL preincubated with DHA or EPA, and then washed and chromium radiolabeled, still exhibited an adhesion inhibition to TNF alpha- and IL-4-treated EC as well as untreated EC. Cytofluorometry and immunoenzymatic analyses indicated that pretreatment of EC with (n-3) PUFAs before their activation significantly reduced the EC-induced expression of vascular cell adhesion molecule 1, whereas the level of expression of intercellular adhesion molecule 1 and E-selectin was not modified. Furthermore, we showed that incubation of PBL with DHA or EPA moderately reduced the level of cell surface expression of L-selectin and leukocyte function-associated antigen 1, but not of very late antigen 4. In all cases, the inhibitory effect of (n-3) PUFAs was specific and dose dependent. In addition, DHA seems to be a more potent inhibitor than EPA, but the two compounds in association had an additive effect. Regardless of the mode of action, this inhibitory effect may explain the protective and ameliorative effects of (n-3) PUFAs on diseases involving chronic inflammatory reaction.

Omega-3 Fatty Acid-Derived Mediators 17(R)-Hydroxy Docosahexaenoic Acid, Aspirin-Triggered Resolvin D1 and Resolvin D2 Prevent Experimental Colitis in Mice

“…Furthermore, our findings are in line with previous studies that have shown that RvE1 and RvD1 reduce PMN transmigration across choroid retinal endothelial cells stimulated with IL-1b and that this effect is dependent on VCAM-1 expression (50). In addition, in vitro incubation with EPA or DHA has been shown to decrease VCAM-1, ICAM-1, and LFA-1 expression in human epithelial cells stimulated with LPS (51).…”

Reduction in Homocysteine by n–3 Polyunsaturated Fatty Acids after 1 Year in a Randomised Double-Blind Study following an Acute Myocardial Infarction: No Effect on Endothelial Adhesion Properties

“…The vast majority of studies suggesting that endothelial dysfunction may be triggered by high levels of Hcy [11][12][13][14][15], and studies demonstrating beneficial effects of n-3 PUFAs on cellular adhesion molecules [34][35][36], are based on cell cultures and in vitro models. In contrast to reports demonstrating beneficial effects of n-3 PUFAs on cell culture studies, serum concentrations of the soluble adhesion molecules E-selectin and VCAM-1 were increased by a daily dose of 5.1 g n-3 PUFAs given to asymptomatic post-PTCA coronary patients [23].…”

Effect of fatty acids on leukocyte function

“…Thus, animals fed diets rich in omega-3 fatty acids (fish oil) and omega-6 fatty acids (olive oil) have decreased expression of LFA-1, ICAM-1 and CD2 (3,31). Pretreatment of lymphocytes with DHA or EPA (omega-3) can reduce the expression of the adhesion molecules Lselectin and LFA-1 (45). The addition of DHA or EPA acids to adhesion assays involving endothelial cells and lymphocytes reduces cell interaction, which is associated with reduced expression of VCAM-1 (45).…”

“…Pretreatment of lymphocytes with DHA or EPA (omega-3) can reduce the expression of the adhesion molecules Lselectin and LFA-1 (45). The addition of DHA or EPA acids to adhesion assays involving endothelial cells and lymphocytes reduces cell interaction, which is associated with reduced expression of VCAM-1 (45).…”

“…-Omega-3-rich diets decrease NK and LAK cell activity (14,23,24). -Omega-3 fatty acids decrease adhesion molecule expression and lymphocyte adhesion to the endothelium (3,31,45).…”