Wallace F A, Neely S J, Miles E A, Calder P C
Institute of Human Nutrition, University of Southampton, Southampton, United Kingdom.
Immunol Cell Biol. 2000 Feb;78(1):40-8. doi: 10.1046/j.1440-1711.2000.00867.x.
In the present study, the effects of feeding mice diets of different fatty acid compositions on the production of TNF-alpha and nitric oxide by lipopolysaccharide-stimulated peritoneal macrophages and on macrophage-mediated cytotoxicity towards L929 and P815 cells were investigated. C57Bl6 mice were fed on a low-fat (LF) diet or on high-fat diets (21% fat by weight), which included coconut oil (CO), olive oil (OO), safflower oil (SO) or fish oil (FO) as the principal fat source. The fatty acid composition of the macrophages was markedly influenced by that of the diet fed. Lipopolysaccharide (LPS)-stimulated macrophages from FO-fed mice showed significantly lower production (up to 80%) of PGE2 than those from mice fed on each of the other diets. There was a significant positive linear correlation between the proportion of arachidonic acid in macrophage lipids and the ability of macrophages, to produce PGE2. Lipopolysaccharide-stimulated TNF-alpha production by macrophages decreased with increasing unsaturated fatty acid content of the diet (i.e. FO < SO < OO < CO < LF). Macrophages from FO-fed mice showed significantly lower production of TNF-alpha than those from mice fed on each of the other diets. Nitrite production was highest for LPS-stimulated macrophages from mice fed on the LF diet. Macrophages from FO-fed mice showed significantly higher production of nitrite than those from mice fed on the OO and SO diets. Compared with feeding the LF diet, feeding the CO, OO or SO diets significantly decreased macrophage- mediated killing of P815 cells (killed by nitric oxide). Fish oil feeding did not alter killing of P815 cells by macrophages, compared with feeding the LF diet; killing of P815 cells was greater after FO feeding than after feeding the other high fat diets. Compared with feeding the LF diet, feeding the OO or SO diets significantly decreased macrophage-mediated killing of L929 cells (killed by TNF). Coconut oil or FO feeding did not alter killing of L929 cells by macrophages, compared with feeding the LF diet. It is concluded that the type of fat in the diet affects macrophage composition and alters the ability of macrophages to produce cytotoxic and immunoregulatory mediators and to kill target tumour cells.
在本研究中，研究了给小鼠喂食不同脂肪酸组成的饮食对脂多糖刺激的腹腔巨噬细胞产生肿瘤坏死因子-α（TNF-α）和一氧化氮的影响，以及对巨噬细胞介导的对L929和P815细胞的细胞毒性的影响。给C57Bl6小鼠喂食低脂（LF）饮食或高脂饮食（按重量计含21%脂肪），其中包括以椰子油（CO）、橄榄油（OO）、红花油（SO）或鱼油（FO）作为主要脂肪来源。所喂食饮食的脂肪酸组成对巨噬细胞的脂肪酸组成有显著影响。来自喂食鱼油的小鼠的脂多糖（LPS）刺激的巨噬细胞显示，与来自喂食其他每种饮食的小鼠的巨噬细胞相比，前列腺素E2（PGE2）的产生显著降低（高达80%）。巨噬细胞脂质中花生四烯酸的比例与巨噬细胞产生PGE2的能力之间存在显著的正线性相关。随着饮食中不饱和脂肪酸含量的增加，脂多糖刺激的巨噬细胞产生的TNF-α减少（即FO < SO < OO < CO < LF）。来自喂食鱼油的小鼠的巨噬细胞显示，与来自喂食其他每种饮食的小鼠的巨噬细胞相比，TNF-α的产生显著降低。喂食LF饮食的小鼠的LPS刺激的巨噬细胞的亚硝酸盐产生最高。来自喂食鱼油的小鼠的巨噬细胞显示，与来自喂食橄榄油和红花油饮食的小鼠的巨噬细胞相比，亚硝酸盐的产生显著更高。与喂食LF饮食相比，喂食CO、OO或SO饮食显著降低了巨噬细胞介导的对P815细胞的杀伤（由一氧化氮杀伤）。与喂食LF饮食相比，喂食鱼油并未改变巨噬细胞对P815细胞的杀伤；喂食鱼油后对P815细胞的杀伤比喂食其他高脂饮食后更大。与喂食LF饮食相比，喂食OO或SO饮食显著降低了巨噬细胞介导的对L929细胞的杀伤（由TNF杀伤）。与喂食LF饮食相比，喂食椰子油或鱼油并未改变巨噬细胞对L929细胞的杀伤。得出的结论是，饮食中的脂肪类型会影响巨噬细胞组成，并改变巨噬细胞产生细胞毒性和免疫调节介质以及杀伤靶肿瘤细胞的能力。
