Basal activation of protein kinase C in rat alveolar macrophages: implications for arachidonate metabolism.
Basal activation of protein kinase C in rat alveolar macrophages: implications for arachidonate metabolism.
复制标题
大鼠肺泡巨噬细胞中蛋白激酶 C 的基础激活：对花生四烯酸代谢的影响。
DOI：
10.1152/ajplung.1991.261.6.l462
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发表时间：
1991
期刊：
影响因子：
--
通讯作者：
Balazovich,K
中科院分区：
文献类型：
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作者：
Peters-Golden,M;McNish,RW;Sporn,PH;Balazovich,K
肺泡巨噬细胞(AM)表现出许多与其他单核巨噬细胞群不同的功能，尽管它们来自一种常见的循环单核细胞前体。然而，到目前为止，AM独特表达的基本信号机制的差异还没有被阐明。蛋白激酶C(PKC)是一种被认为在调节巨噬细胞功能中起重要作用的信号转导机制，但对AM的研究知之甚少本研究比较了培养的大鼠AM和大鼠腹膜巨噬细胞(PM)中PKC的激活状态，并探讨了活性PKC对这两种细胞中花生四烯酸(AA)代谢的调节作用。通过组蛋白磷酸化实验评估，与PM相反，静息AM表现出对PKC的结构性激活，主要的PKC活性定位于膜部分。离子载体A23187刺激的AA释放和代谢可通过耗尽或抑制AM中的细胞PKC活性而不是PM中的PKC活性来减弱相反，A23187刺激的AA代谢通过激活PKC在PM比AM更大程度地增强来自两种细胞类型的结果表明，PKC激活特别上调了5-脂氧合酶途径。我们得出的结论是，PKC的激活是巨噬细胞在肺泡间隙中特有的，这一特性以及PKC的下调对至少一种重要的巨噬细胞功能的调节具有深远的影响，即生物活性二十烷类化合物的合成。
Alveolar macrophages (AM) exhibit numerous functional differences from other mononuclear phagocyte populations, even though they are derived from a common circulating monocytic precursor. Yet no differences in fundamental signaling mechanisms uniquely expressed by AM have been elucidated to date. Protein kinase C (PKC) is one signal transduction mechanism thought to have an important role in regulating macrophage function and about which little information exists for AM. This study was undertaken to assess the state of activation of PKC in cultured resident rat AM compared with resident rat peritoneal macrophages (PM) and the means by which active PKC regulates arachidonic acid (AA) metabolism in the two cell types. As assessed by a histone phosphorylation assay, resting AM, in contrast to PM, exhibited constitutive activation of PKC as evidenced by localization of a majority of PKC activity to the membrane fraction. Ionophore A23187-stimulated release and metabolism of AA were attenuated by depletion of or inhibition of cellular PKC activity in AM but not in PM. In contrast, A23187-stimulated AA metabolism was augmented by activation of PKC to a greater extent in PM than in AM. Results from both cell types indicated that the 5-lipoxygenase pathway was particularly upregulated by PKC activation. We conclude that activation of PKC occurs uniquely during macrophage residence in the alveolar space and that this property as well as the downregulation of PKC which results have profound consequences for the regulation of at least one important macrophage function, the synthesis of bioactive eicosanoids.