Department of Pediatrics, Centro di Riferimento Fibrosi Cistica Regione Lazio, Università La Sapienza, Viale Regina Elena 324, 00161, Rome, Italy.
Inflamm Res. 2009 Oct;58(10):677-85. doi: 10.1007/s00011-009-0035-5. Epub 2009 Mar 31.
It is believed that correction of membrane fatty acid deficiency in cystic fibrosis (CF) downregulates the synthesis of proinflammatory mediators. We tested the hypothesis that an increase of the proportion of docosahexaenoic acid (DHA) in the membrane in vitro changes the neutrophil response to Pseudomonas aeruginosa lipopolysaccharide (LPS).
Treatment with DHA increased the secretion of interleukin(IL)-1|alpha| by CF neutrophils, but the secretion of other cytokines, CD11b expression, and arachidonic acid (AA) release were not affected either in CF or control (CT) neutrophils. Both with and without DHA, only one out of eight CF neutrophils responded to LPS with an increase of released AA, while five out of seven CT cells released more AA (CF vs. CT P < 0.05 by Fisher test).
These results indicate that in neutrophils the beneficial effects of DHA on immune response are not directly related to the generation of proinflammatory precursors, and suggest that in CF the lower neutrophil AA generation in response to activation could cause insufficient production of lipid mediators involved in the resolution of lung inflammation.
据信囊性纤维化(CF)中膜脂肪酸缺乏的纠正会下调促炎介质的合成。我们检验了这样一个假设,即在体外增加膜中二**烯酸(DHA)的比例会改变中性粒细胞对铜绿假单胞菌脂多糖(LPS)的反应。
用 DHA 处理增加了 CF 中性粒细胞白细胞介素(IL)-1|alpha|的分泌,但 CF 或对照(CT)中性粒细胞的其他细胞因子分泌、CD11b 表达和花生四烯酸(AA)释放均不受影响。DHA 存在或不存在时,只有 8 个 CF 中性粒细胞中的 1 个对 LPS 反应释放更多的 AA,而 7 个 CT 细胞中有 5 个释放更多的 AA(CF 与 CT 通过 Fisher 检验 P < 0.05)。
这些结果表明,在中性粒细胞中,DHA 对免疫反应的有益作用与产生促炎前体不直接相关,并表明在 CF 中,激活后中性粒细胞 AA 生成减少可能导致参与肺炎症消退的脂质介质产生不足。