Neutrophil unsaturated fatty acid release by GM-CSF is impaired in cystic fibrosis
Neutrophil unsaturated fatty acid release by GM-CSF is impaired in cystic fibrosis
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DOI：
10.1186/1476-511x-9-129
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发表时间：
2010-11-08
影响因子：
4.5
通讯作者：
Quattrucci, Serena
中科院分区：
文献类型：
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作者：
Bravo, Elena;Napolitano, Mariarosaria;Quattrucci, Serena
囊性纤维化(CF)的炎症调节失调归因于由多不饱和脂类衍生的炎性介质产生的改变。与花生四烯酸(AA)级联相比，对二十二碳六烯酸(DHA)膜释放的调控知之甚少。我们用[(3)H]AA或[(14)C]DHA分别作为AA和DHA释放的标志物，比较了对照组(CT)和CF患者中性粒细胞DHA和AA释放的数据。粒细胞-巨噬细胞集落刺激因子可刺激CT中性粒细胞释放DHA，但不能刺激中性粒细胞释放。比较发现，CT刺激后释放的[(14)C]DHA和[(3)H]AA均高于CF中性粒细胞。由于DHA来源的生物活性介质是分解因子，而AA来源的生物活性介质既有促炎作用，又有抗炎作用，这些结果表明，CF与减少脂氧化分解介质的多不饱和脂肪酸前体的释放有关。这导致了一种假说，即溶解因子产生的缺陷可能导致了CF的炎性失调过程。此外，所使用的方法可能有助于提高对炎症调节和消退的认识。
Dysregulated inflammation in cystic fibrosis (CF) is attributed to an altered production of inflammatory mediators derived from polyunsaturated lipids. In comparison to the arachidonic acid (AA) cascade, little is known about the modulation of docosahexaenoic acid (DHA) membrane release. We compared data on neutrophil DHA- and AA-release from both control (CT) and patients with CF using [(3)H]AA or [(14)C]DHA as a markers for, respectively, AA and DHA-release. Granulocyte-macrophage-colony stimulating factor stimulated DHA release from CT, but not CF, neutrophils. Comparison showed that both [(14)C]DHA and [(3)H]AA liberated after stimulation was higher in CT than in CF neutrophils. Since bioactive mediators derived from DHA are resolving factors and those derived from AA are both pro-and anti-inflammatory, these results suggest that CF is associated with a reduction of the release of PUFA-precursors of lipooxygenated resolving mediators. This leads to the hypothesis that defects in the resolving factors production could contribute to the inflammatory dysregulated processes in CF. Furthermore, the methodology used may help to improve knowledge on the regulation and resolution of inflammation.