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首页> 外文期刊>Molecular and Cellular Biology >Molecular Mechanisms of N-Formyl-Methionyl-Leucyl-Phenylalanine-Induced Superoxide Generation and Degranulation in Mouse Neutrophils: Phospholipase D Is Dispensable
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Molecular Mechanisms of N-Formyl-Methionyl-Leucyl-Phenylalanine-Induced Superoxide Generation and Degranulation in Mouse Neutrophils: Phospholipase D Is Dispensable

机译：N-甲酰基-甲硫酰基-亮氨酰-苯丙氨酸诱导的小鼠嗜中性粒细胞中超氧化物生成和脱粒的分子机制：磷脂酶D是可有可无的。

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Phospholipase D (PLD), which produces the lipid messenger phosphatidic acid (PA), has been implicated in superoxide generation and degranulation in neutrophils. The basis for this conclusion is the observation that primary alcohols, which interfere with PLD-catalyzed PA production, inhibit these neutrophil functions. However, off-target effects of primary alcohols cannot be totally excluded. Here, we generated PLD?/? mice in order to reevaluate the involvement of PLD in and investigate the molecular mechanisms of these neutrophil functions. Surprisingly, N-formyl-methionyl-leucyl-phenylalanine (fMLP) induced these functions in PLD?/? neutrophils, and these functions were suppressed by ethanol. These results indicate that PLD is dispensable for these neutrophil functions and that ethanol nonspecifically inhibits them, warning against the use of primary alcohols as specific inhibitors of PLD-mediated PA formation. The calcium ionophore ionomycin and the membrane-permeative compound 1-oleoyl-2-acetyl-sn-glycerol (OADG) synergistically induced superoxide generation. On the other hand, ionomycin alone induced degranulation, which was further augmented by OADG. These results demonstrate that conventional protein kinase C (cPKC) is crucial for superoxide generation, and a Ca2+-dependent signaling pathway(s) and cPKC are involved in degranulation in mouse neutrophils.
机译：产生脂质信使磷脂酸（PA）的磷脂酶D（PLD）与嗜中性粒细胞的超氧化物生成和脱粒有关。该结论的基础是观察到，干扰PLD催化的PA生成的伯醇会抑制这些中性粒细胞功能。但是，不能完全排除伯醇的脱靶效应。在这里，我们生成了 PLD ？/？小鼠，以重新评估PLD的参与并研究这些嗜中性粒细胞功能的分子机制。出乎意料的是， N -甲酰基-甲硫酰基-亮氨酰-苯丙氨酸（fMLP）在嗜中性粒细胞中诱导 PLD ？/？这些功能，并且这些功能被抑制用乙醇。这些结果表明PLD对于这些嗜中性粒细胞功能是可有可无的，并且乙醇非特异性地抑制它们，警告不要将伯醇用作PLD介导的PA形成的特异性抑制剂。钙离子载体离子霉素和膜渗透性化合物1-油酰基-2-乙酰基-sn -甘油（OADG）协同诱导了超氧化物的产生。另一方面，仅离子霉素可引起脱粒，而OADG进一步加剧了脱粒。这些结果表明，常规的蛋白激酶C（cPKC）对于产生超氧化物至关重要，并且Ca 2 + 依赖的信号通路和cPKC参与了小鼠嗜中性粒细胞的脱粒。

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