Khalfoun B, Thibault G, Bardos P, Lebranchu Y
Groupe Interactions Hôte-Greffon, Faculté de Médecine, Tours, France.
Transplantation. 1996 Dec 15;62(11):1649-57. doi: 10.1097/00007890-199612150-00020.
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.
膳食补充富含大量长链ω-3（(n-3)）多不饱和脂肪酸（PUFA）的鱼油，特别是二十二碳六烯酸（DHA）和二十碳五烯酸（EPA），最近已显示出对以慢性炎症反应为特征的疾病具有保护和改善作用。血管内皮、单核细胞和细胞因子之间的相互作用是慢性移植排斥等炎症过程中的关键步骤。因此，我们研究了DHA和EPA对培养的外周血淋巴细胞（PBL）与人内皮细胞（EC）的黏附以及EC黏附分子及其在PBL上的反受体表达的影响。在黏附试验中添加DHA或EPA可显著降低PBL对未处理的EC以及肿瘤坏死因子-α（TNFα）、白细胞介素（IL）4和脂多糖刺激的EC的黏附。当EC用(n-3) PUFA预处理18小时、洗涤后再用TNFα、IL-4或脂多糖刺激时，与对照组相比，PBL黏附也显著降低。我们还表明，用DHA或EPA预孵育PBL，然后洗涤并进行铬放射性标记，其对TNFα和IL-4处理的EC以及未处理的EC仍表现出黏附抑制作用。细胞荧光分析和免疫酶分析表明，在激活前用(n-3) PUFA预处理EC可显著降低EC诱导的血管细胞黏附分子1的表达，而细胞间黏附分子1和E-选择素的表达水平未改变。此外，我们表明用DHA或EPA孵育PBL可适度降低L-选择素和白细胞功能相关抗原1的细胞表面表达水平，但对极晚期抗原4的表达水平无影响。在所有情况下，(n-3) PUFA的抑制作用是特异性的且呈剂量依赖性。此外，DHA似乎比EPA是更有效的抑制剂，但这两种化合物联合使用具有相加作用。无论作用方式如何这种抑制作用可能解释了(n-3) PUFA对涉及慢性炎症反应疾病的保护和改善作用。
