Macrophage colony stimulating factor activates phosphatidylcholine hydrolysis by cytoplasmic phospholipase A2.
Macrophage colony stimulating factor activates phosphatidylcholine hydrolysis by cytoplasmic phospholipase A2.
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巨噬细胞集落刺激因子通过细胞质磷脂酶 A2 激活磷脂酰胆碱水解。
DOI：
10.1002/j.1460-2075.1992.tb05598.x
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发表时间：
1992
期刊：
影响因子：
--
通讯作者：
Kufe,D
中科院分区：
文献类型：
--
作者：
Nakamura,T;Lin,LL;Kharbanda,S;Knopf,J;Kufe,D
巨噬细胞集落刺激因子（M-CSF）是单核细胞增殖和分化所必需的。先前的研究表明，M-CSF 刺激与磷脂酰胆碱 (PC) 水解以及二酰甘油 (DAG) 和磷酸胆碱的形成增加有关。目前的工作扩展了这些结果，证明用 M-CSF 处理人单核细胞与细胞质 Ca(2+) 依赖性活性的增加相关，该活性将 1-棕榈酰,2-花生四烯酰 PC 水解为花生四烯酸。 PC 的这种水解与溶血磷脂酰胆碱产量的增加相关，这一发现表明 M-CSF 刺激细胞质磷脂酶 A2 (cPLA2) 活性。 M-CSF 诱导 cPLA2 基因表达的证据支持了这些结果。 M-CSF 诱导的 cPLA2 mRNA 水平增加是双相的，并且与 cPLA2 活性的快速（30-60 分钟）和延迟（24-72 小时）增加相对应。结果表明，M-CSF 对 cPLA2 表达的影响至少部分是由 cPLA2 转录物的转录后稳定性控制的。 M-CSF 治疗还与 cPLA2 蛋白磷酸化相关的发现进一步表明该酶的表达在多个水平上受到调节。最后，前列腺素 (PG) 合成的增加支持 cPLA2 活性和花生四烯酸释放的刺激。在这方面，PGE2 和 PGF2 α 的水平因 M-CSF 的反应而增加。综上所述，这些结果表明 M-CSF 通过诱导 cPLA2 活性并从而形成类二十烷酸来刺激人单核细胞中的 PC 水解。
The macrophage colony stimulating factor (M‐CSF) is required for the proliferation and differentiation of monocytes. Previous studies have demonstrated that M‐CSF stimulation is associated with phosphatidylcholine (PC) hydrolysis and increased formation of both diacylglycerol (DAG) and phosphorylcholine. The present work extends those results by demonstrating that treatment of human monocytes with M‐CSF is associated with increases in a cytoplasmic Ca(2+)‐dependent activity which hydrolyzes 1‐palmitoyl,2‐arachidonoyl PC to arachidonic acid. The finding that this hydrolysis of PC is associated with increases in production of lysophosphatidylcholine indicates that M‐CSF stimulates a cytoplasmic phospholipase A2 (cPLA2) activity. These results are supported by the demonstration that M‐CSF induces cPLA2 gene expression. M‐CSF‐induced increases in cPLA2 mRNA levels were biphasic and corresponded with rapid (30–60 min) and delayed (24–72 h) increases in cPLA2 activity. The results demonstrate that this effect of M‐CSF on cPLA2 expression is controlled at least in part by post‐transcriptional stabilization of cPLA2 transcripts. The finding that M‐CSF treatment is also associated with phosphorylation of the cPLA2 protein further suggests that expression of this enzyme is regulated at multiple levels. Finally, the stimulation of cPLA2 activity and arachidonate release is supported by increases in prostaglandin (PG) synthesis. In this regard, levels of both PGE2 and PGF2 alpha were increased in response to M‐CSF. Taken together, these results indicate that M‐CSF stimulates PC hydrolysis in human monocytes by inducing cPLA2 activity and thereby formation of eicosanoids.