DIETARY OMEGA-3 POLYUNSATURATED FATTY-ACIDS INHIBIT PHOSPHOINOSITIDE FORMATION AND CHEMOTAXIS IN NEUTROPHILS
DIETARY OMEGA-3 POLYUNSATURATED FATTY-ACIDS INHIBIT PHOSPHOINOSITIDE FORMATION AND CHEMOTAXIS IN NEUTROPHILS
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DOI：
10.1172/jci116245
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发表时间：
1993-02-01
影响因子：
15.9
通讯作者：
ROBINSON, DR
中科院分区：
文献类型：
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作者：
SPERLING, RI;BENINCASO, AI;ROBINSON, DR
早期的研究表明，饮食中补充omega-3多不饱和脂肪酸（PUFA）可以减弱中性粒细胞的趋化反应和钙离子载体刺激中性粒细胞产生白三烯（LT） B4；然而，这些影响的机制和关系尚未得到检验。研究人员对8名健康个体的中性粒细胞和单核细胞进行了检测，分别在每天补充20 g SuperEPA（提供9.4 g二十碳五烯酸（EPA）和5 g二十二碳六烯酸）之前和之后的3周和10周。在Boyden微室中评估的LTB4的最大中性粒细胞趋化反应在3周后下降了69%，在10周后下降了93%。LTB4刺激下[H-3]肌醇标记的中性粒细胞形成的[H-3]三磷酸肌醇（IP3）在3周后（[H-3]释放量为0.033+/-0.013%，平均+/-SEM）减少了71%，在10周后（0.011+/-0.011%）从饲前（0.114+/-0.030%）减少了90% （HPLC解析后的β闪烁计数）。ltb4刺激的中性粒细胞趋化性与IP3形成显著相关（P < 0.0001）；各响应与中性粒细胞磷脂酰肌醇（PI）池EPA含量呈密切负相关（P = 0.0003和P = 0.0005）。在研究过程中，高亲和力和低亲和力LTB4受体对中性粒细胞的亲和力和密度以及LTB4介导的双甘油酯形成都没有明显变化。在血小板活化因子（PAF）活化的中性粒细胞中也观察到类似的结果。在钙离子载体刺激的中性粒细胞中，LTB4和LTB5的总和形成被选择性地抑制，在酶蛋白刺激的中性粒细胞中，LTB4和LTB5的总和形成也被抑制。在钙离子载体刺激的中性粒细胞和酶蛋白刺激的中性粒细胞中，LTB4和LTB5的总形成的抑制与PI池中EPA的含量没有显著的相关性。数据表明，饮食中补充omega-3 PUFA可以抑制中性粒细胞炎症反应的自身扩增，通过LTA环氧化物水解酶失活来减少LTB4的形成，并通过减少pi选择性磷脂酶c形成IP3来抑制LTB4-（和PAF）刺激的趋化性，从而抑制pi特异性水平的信号转导。这初步证明了饮食中补充omega-3 PUFA可以抑制pi特异性水平的信号转导人体内的磷脂酶C
Earlier studies demonstrated that dietary omega-3 polyunsaturated fatty acid (PUFA) supplementation attenuates the chemotactic response of neutrophils and the generation of leukotriene (LT) B4 by neutrophils stimulated with calcium ionophore; however, the mechanisms and relationship of these effects were not examined. Neutrophils and monocytes from eight healthy individuals were examined before and after 3 and 10 wk of dietary supplementation with 20 g SuperEPA daily, which provides 9.4 g eicosapentaenoic acid (EPA) and 5 g docosahexaenoic acid. The maximal neutrophil chemotactic response to LTB4, assessed in Boyden microchambers, decreased by 69% after 3 wk and by 93% after 10 wk from prediet values. The formation of [H-3]inositol tris-phosphate (IP3) by [H-3]inositol-labeled neutrophils stimulated by LTB4 decreased by 71% after 3 wk (0.033+/-0.013% [H-3] release, mean+/-SEM) and by 90% after 10 wk (0.011+/-0.011%) from prediet values (0.114+/-0.030%) as quantitated by beta-scintillation counting after resolution on HPLC. LTB4-stimulated neutrophil chemotaxis and IP3 formation correlated significantly (P < 0.0001); each response correlated closely and negatively with the EPA content of the neutrophil phosphatidylinositol (PI) pool (P = 0.0003 and P = 0.0005, respectively). Neither the affinities and densities of the high and low affinity LTB4 receptors on neutrophils nor LTB4-mediated diglyceride formation changed appreciably during the study. Similar results were observed in neutrophils activated with platelet-activating factor (PAF). The summed formation of LTB4 plus LTB5 was selectively inhibited in calcium ionophore-stimulated neutrophils and was also inhibited in zymosan-stimulated neutrophils. The inhibition of the summed formation of LTB4 plus LTB5 in calcium ionophore-stimulated neutrophils and in zymosan-stimulated neutrophils did not correlate significantly with the EPA content of the PI pool. The data indicate that dietary omega-3 PUFA supplementation inhibits the autoamplification of the neutrophil inflammatory response by decreasing LTB4 formation through the inactivation of the LTA epoxide hydrolase and independently by inhibiting LTB4- (and PAF) stimulated chemotaxis by attenuating the formation of IP3 by the PI-selective phospholipase C. This is the initial demonstration that dietary omega-3 PUFA supplementation can suppress signal transduction at the level of the PI-specific phospholipase C in humans.