Free fatty acids enhance hypochlorous acid production by activated neutrophils.
Free fatty acids enhance hypochlorous acid production by activated neutrophils.
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发表时间：
1994-07
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通讯作者：
M. Qian;J. Eaton
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作者：
M. Qian;J. Eaton
活化的多形核中性粒细胞（pmn）可能有助于长期吸烟者慢性阻塞性肺疾病的发生。然而，目前尚不清楚烟雾中的哪些元素在引发这种进行性肺损伤或影响炎症细胞（如PMNS）的活动中起重要作用。我们早些时候在香烟烟雾的有机浓缩物中发现了一些物质，这些物质可以结合亚铁并将金属转化为有机相。这些物质后来被确定为饱和游离脂肪酸，主要是棕榈酸和硬脂酸（16:0和18:0）。我们现在报道脂肪酸对PMNs氧化代谢的影响的研究。与大多数早期报道一致，我们发现饱和脂肪酸对PMN氧化代谢的直接影响很小。然而，微摩尔量的游离脂肪酸会使PMNs受少量肉豆蔻酸佛酚刺激产生的次氯酸（HOCl）增加一倍以上。当PMNs受到1,2-二辛烷酰-sn-甘油和1-油基-2-乙酰基-sn-甘油（也被认为是蛋白激酶C的激动剂）的刺激时，也会出现类似的脂肪酸介导的HOCl生成增加，但当细胞受到钙离子载体A23187、甲酰化三肽f-met-leu-phe或调理酶san的刺激时，HOCl生成不会增加。脂肪酸介导的PMN HOCl生成的增强显然是由于受刺激的PMN释放的髓过氧化物酶增加。此外，在游离脂肪酸存在的情况下，受刺激的pmn对培养的水貂肺上皮细胞具有更大的细胞毒性，这种毒性被HOCl清道夫阻断。这些结果表明，烟草烟雾中相对大量的游离脂肪酸可能会放大pmn介导的对吸烟者肺部的氧化损伤。
Activated polymorphonuclear neutrophils (PMNs) may contribute to the genesis of chronic obstructive lung disease in long-term cigarette smokers. However, it is not presently known which elements in smoke are important in triggering this progressive pulmonary damage or in affecting the activities of inflammatory cells such as PMNS. We earlier found substances in organic concentrates of cigarette smoke that bound ferrous iron and transferred the metal into organic phases. These substances were later identified as saturated free fatty acids, predominantly palmitic and stearic acids (16:0 and 18:0). We now report investigations of the effects of fatty acids on the oxidative metabolism of PMNs. In accord with most earlier reports, we find that saturated fatty acids have little direct effect on PMN oxidative metabolism. However, micromolar amounts of free fatty acids will more than double production of hypochlorous acid (HOCl) by PMNs stimulated with small amounts of phorbol myristate acetate. Similar fatty acid-mediated increases in HOCl production also occur when PMNs are stimulated with 1,2-dioctanoyl-sn-glycerol and 1-oleoyl-2-acetyl-sn-glycerol (also thought to be agonists of protein kinase C) but not when cells are stimulated with the calcium ionophore A23187, the formylated tripeptide f-met-leu-phe, or opsonized zymosan. Fatty acid-mediated enhancement of PMN HOCl production evidently arises from increased release of myeloperoxidase from stimulated PMNs. Furthermore, in the presence of free fatty acids, stimulated PMNs are much more cytotoxic toward cultured mink lung epithelial cells, a toxicity that is blocked by scavengers of HOCl. These results suggest that the relatively large amounts of free fatty acids present in tobacco smoke may act to amplify PMN-mediated oxidative damage to the lungs of smokers.