Changes in PKC isoforms in human alveolar macrophages compared with blood monocytes.
Changes in PKC isoforms in human alveolar macrophages compared with blood monocytes.
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DOI：
10.1152/ajplung.1998.275.2.l389
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发表时间：
1998-08
期刊：
影响因子：
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通讯作者：
M. Monick;A. B. Carter;G. Gudmundsson;L. Geist;G. Hunninghake
中科院分区：
文献类型：
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作者：
M. Monick;A. B. Carter;G. Gudmundsson;L. Geist;G. Hunninghake
肺泡巨噬细胞在宿主防御和肺部其他类型的炎症过程中起重要作用。这些细胞与它们的前体细胞，血液单核细胞相比，表现出许多功能上的改变。为了评估这些功能差异的潜在机制，我们评估了蛋白激酶C（PKC）亚型的表达。我们发现，增加钙依赖性PKC亚型的单核细胞相比，肺泡巨噬细胞。我们还发现，与单核细胞相比，肺泡巨噬细胞中的钙离子非依赖性亚型的差异表达。PKC活化的一个结果是促分裂原活化蛋白（MAP）激酶途径的表达增加。因此，我们也评估了激活的MAP激酶细胞外信号调节激酶（ERK）2的佛波醇酯佛波醇12-肉豆蔻酸酯13-乙酸酯（PMA）。PMA激活肺泡巨噬细胞和单核细胞中的ERK 2激酶;然而，与肺泡巨噬细胞相比，单核细胞始终显示出PMA对ERK 2激酶的显著更大激活。PKC激活和随后的ERK激酶激活的另一个已知结果是转录因子激活蛋白-1（AP-1）的激活。我们评估了PMA在单核细胞和巨噬细胞中对AP-1的激活。我们发现很少检测到激活AP-1，在凝胶迁移试验中评估，在肺泡巨噬细胞，而单核细胞显示出大量激活AP-1的PMA。这些研究表明，肺泡巨噬细胞和血液单核细胞中PKC亚型的差异表达与细胞中重要的功能改变有关。
Alveolar macrophages play an important role in host defense and in other types of inflammatory processes in the lung. These cells exhibit many alterations in function compared with their precursor cells, blood monocytes. To evaluate a potential mechanism for these differences in function, we evaluated expression of protein kinase C (PKC) isoforms. We found an increase in Ca2+-dependent PKC isoforms in monocytes compared with alveolar macrophages. We also found differential expression of the Ca2+-independent isoforms in alveolar macrophages compared with monocytes. One consequence of the activation of PKC can be increased expression of mitogen-activated protein (MAP) kinase pathways. Therefore, we also evaluated activation of the MAP kinase extracellular signal-regulated kinase (ERK) 2 by the phorbol ester phorbol 12-myristate 13-acetate (PMA). PMA activated ERK2 kinase in both alveolar macrophages and monocytes; however, monocytes consistently showed a significantly greater activation of ERK2 kinase by PMA compared with alveolar macrophages. Another known consequence of the activation of PKC and subsequent activation of ERK kinase is activation of the transcription factor activator protein-1 (AP-1). We evaluated the activation of AP-1 by PMA in both monocytes and macrophages. We found very little detectable activation of AP-1, as assessed in a gel shift assay, in alveolar macrophages, whereas monocytes showed a substantial activation of AP-1 by PMA. These studies show that the differential expression of PKC isoforms in alveolar macrophages and blood monocytes is associated with important functional alterations in the cells.