Sethi S, Eastman A Y, Eaton J W
Division of Experimental Pathology, Albany Medical College, NY, USA.
J Lab Clin Med. 1996 Jul;128(1):27-38. doi: 10.1016/s0022-2143(96)90111-0.
Diets rich in marine fish oil may protect against cardiovascular disease. Although the mechanisms involved in such protection are not known, fish oils have been reported to exert anti-inflammatory actions. For example, dietary fish oil supplementation was observed to profoundly decrease the numbers of monocytic cells adherent to endothelium overlying atherosclerotic lesions in pigs. We have therefore investigated the possibility that fish oil components-particularly n-3 polyunsaturated fatty acids (PUFAs)-might inhibit phagocyte-endothelium interactions. We have found that binding of a monocytic cell line (U937) to cultured endothelium (with cell adhesion molecules up-regulated by exposure to lipopolysaccharide (LPS), interleukin-1 alpha, tumor necrosis factor-alpha, or phorbol myristate acetate (PMA) is greatly decreased by pre-exposure of endothelial cells to n-3 and other PUFAs that are incidentally or purposefully oxidized; unoxidized PUFAs are completely ineffective. Decreased monocyte adherence probably derives from diminished up-regulation of endothelial cell adherence molecules VCAM-1 and ELAM-1. Oxidized n-3 PUFAs prevent LPS- or PMA-induced activation of transcription factor NF-kappa B and the consequent induction of mRNA for both cell adhesion molecules. Hydroperoxy fatty acids are the active principle in oxidized PUFAs because the activity (1) is predominantly organic soluble, (2) is obliterated by pretreatment of oxidized material with chemical reducing agents, and (3) is diminished by enzymatic reduction of organic hydroperoxides with glutathione/glutathione peroxidase. We speculate that this suppression of phagocyte-endothelium interactions by oxidized PUFAs may help explain the anti-inflammatory and possible anti-atherogenic effects of diets rich in fish oil. Perhaps more importantly, this modulation of endothelial cell adhesion molecule expression by oxidized lipids may represent a natural mechanism whereby inflammation-mediated oxidation of endothelial PUFAs may retard ingress of phagocytes and thereby prevent unrestrained phlogistic responses.
富含海洋鱼油的饮食可能预防心血管疾病。尽管这种保护作用的机制尚不清楚，但据报道鱼油具有抗炎作用。例如，观察到在猪的饮食中补充鱼油可显著减少粘附在动脉粥样硬化病变上方内皮细胞上的单核细胞数量。因此，我们研究了鱼油成分，特别是n-3多不饱和脂肪酸（PUFAs）可能抑制吞噬细胞与内皮细胞相互作用的可能性。我们发现，单核细胞系（U937）与培养的内皮细胞（通过暴露于脂多糖（LPS）、白细胞介素-1α、肿瘤坏死因子-α或佛波酯（PMA）上调细胞粘附分子）的结合，在内皮细胞预先暴露于n-3和其他偶然或有意氧化的PUFAs后会大大降低；未氧化的PUFAs则完全无效。单核细胞粘附减少可能源于内皮细胞粘附分子VCAM-1和ELAM-1上调的减少。氧化的n-3 PUFAs可阻止LPS或PMA诱导的转录因子NF-κB的激活以及随后两种细胞粘附分子mRNA的诱导。氢过氧脂肪酸是氧化PUFAs中的活性成分，因为其活性（1）主要为有机可溶性，（2）被用化学还原剂预处理氧化物质所消除，（3）通过用谷胱甘肽/谷胱甘肽过氧化物酶对有机氢过氧化物进行酶促还原而降低。我们推测，氧化PUFAs对吞噬细胞与内皮细胞相互作用的这种抑制作用可能有助于解释富含鱼油饮食的抗炎和可能的抗动脉粥样硬化作用。也许更重要的是，氧化脂质对内皮细胞粘附分子表达的这种调节可能代表一种自然机制，即炎症介导的内皮PUFAs氧化可能会延缓吞噬细胞的进入，从而防止无节制的炎症反应。
