Bates E J, Ferrante A, Smithers L, Poulos A, Robinson B S
Department of Immunology, Women's and Children's Hospital, Adelaide, Australia.
Atherosclerosis. 1995 Aug;116(2):247-59. doi: 10.1016/0021-9150(95)05553-9.
Neutrophils have been implicated in ischaemic heart disease, unstable angina pectoris and acute myocardial infarction. Alterations in dietary levels of specific 18- and 20-carbon polyunsaturated fatty acids have significant clinical benefits in cardiovascular disease. However, to date there has been no concerted effort to identify the structural basis for polyunsaturated fatty acid-induced alterations in key neutrophil functions. We have investigated the influence of fatty acid structure and involvement of lipoxygenase/cyclooxygenase pathways on fatty acid-induced neutrophil functions. When neutrophils were incubated with 18-carbon fatty acids containing one to four double bonds (10-33 mumol/l), a significant increase in adherence and release of specific granule constituents occurred compared with control cells. In general, as the number of double bonds in the 18-carbon fatty acid increased, so did its ability to stimulate these functions. There was less stimulation of adherence and specific granule release by 18:3(n-3) than its isomer 18:3(n-6). Smaller effects were seen on azurophilic granule release. A further increase in adherence and degranulation was observed with increasing carbon chain length (20:3(n-6) and 20:4(n-6)). Differences were found in the ability of isomers of 20:3 to stimulate neutrophil function. Of the fatty acids tested only 20:4(n-6) was able to induce significant neutrophil-mediated endothelial detachment. Introduction of either internal hydroperoxy or hydroxyl groups into 20:4(n-6) abolished its adherence stimulating activity and considerably reduced its ability to stimulate release of both specific and azurophilic granules. Preincubation of neutrophils with either lipoxygenase (caffeic acid) or cyclooxygenase (indomethacin) inhibitors had no effect on 20:4(n-6) stimulated function. These studies show that the number and position of double bonds, carbon chain length and oxidation state can be critical to the neutrophil stimulatory properties of these fatty acids.
中性粒细胞与缺血性心脏病、不稳定型心绞痛和急性心肌梗死有关。特定18碳和20碳多不饱和脂肪酸饮食水平的改变在心血管疾病中具有显著的临床益处。然而，迄今为止，尚未有人齐心协力确定多不饱和脂肪酸诱导关键中性粒细胞功能改变的结构基础。我们研究了脂肪酸结构以及脂氧合酶/环氧化酶途径的参与对脂肪酸诱导的中性粒细胞功能的影响。当中性粒细胞与含有1至4个双键的18碳脂肪酸（10 - 33 μmol/l）一起孵育时，与对照细胞相比，特定颗粒成分的黏附及释放显著增加。一般来说，随着18碳脂肪酸双键数量的增加，其刺激这些功能的能力也增强。18:3(n - 3)对黏附和特定颗粒释放的刺激作用小于其异构体18:3(n - 6)。对嗜天青颗粒释放的影响较小。随着碳链长度增加（20:3(n - 6)和20:4(n - 6)），黏附和脱颗粒进一步增加。发现20:3异构体刺激中性粒细胞功能的能力存在差异。在所测试的脂肪酸中，只有20:4(n - 6)能够诱导显著的中性粒细胞介导的内皮细胞脱离。将内部氢过氧基或羟基引入20:4(n - 6)会消除其黏附刺激活性，并大大降低其刺激特定颗粒和嗜天青颗粒释放的能力。用脂氧合酶（咖啡酸）或环氧化酶（吲哚美辛）抑制剂对中性粒细胞进行预孵育，对20:4(n - 6)刺激的功能没有影响。这些研究表明，双键的数量和位置、碳链长度以及氧化状态对于这些脂肪酸的中性粒细胞刺激特性可能至关重要。
