Differential expression of PDE4 cAMP phosphodiesterase isoforms in inflammatory cells of smokers with COPD, smokers without COPD, and nonsmokers
Differential expression of PDE4 cAMP phosphodiesterase isoforms in inflammatory cells of smokers with COPD, smokers without COPD, and nonsmokers
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DOI：
10.1152/ajplung.00384.2003
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发表时间：
2004-08-01
影响因子：
4.9
通讯作者：
Van Heeke, G
中科院分区：
文献类型：
--
作者：
Barber, R;Baillie, GS;Van Heeke, G
一组15种cAMP磷酸二酯酶亚型的表达谱测定与慢性阻塞性肺疾病（COPD）相关的炎性细胞类型。特别是，对患有和不患有COPD的吸烟者的支气管肺泡巨噬细胞、外周血单核细胞、T淋巴细胞和中性粒细胞的表达谱进行了比较。还分析了非吸烟者外周血单核细胞、T淋巴细胞和中性粒细胞的磷酸二酯酶表达谱，并与吸烟者进行了比较。在所有受试者的T细胞、单核细胞和巨噬细胞中，定性RT-PCR鉴定了PDE 4A 10、PDE 4A 7、PDE 4 B1、PDE 4 B2、PDE 4D 1和PDE 4D 2亚型的转录物以及PDE 3B和PDE 7A的转录物。在研究的任何细胞类型中均未观察到PDE 4 B3和PDE 4D 4的转录本。除T细胞外，在所有分析的细胞中均检测到PDE 4C。长PDE 4A 4、PDE 4D 3和PDE 4D 5亚型表现出细胞类型特异性表达模式。半定量和实时定量RT-PCR用于分析疾病状态之间和细胞类型之间的差异表达。与对照吸烟者相比，患有COPD的吸烟者的肺巨噬细胞中PDE 4A 4显着上调。此外，PDE 4A 4以及PDE 4 B2转录检测到吸烟者的外周血单核细胞与非吸烟者相比，在更高的金额。最后，PDE 4D 5和PDE 4C差异调节肺巨噬细胞相比，单核细胞相同的主题，无论疾病状态。获得的数据表明，PDE 4A 4可能是相关的巨噬细胞特异性抗炎目标的COPD。
The expression profile of a panel of 15 cAMP phosphodiesterase isoforms was determined for inflammatory cell types of relevance to chronic obstructive pulmonary disease ( COPD). In particular, the expression profiles for bronchoalveolar macrophages, peripheral blood monocytes, T lymphocytes, and neutrophils from smokers with and without COPD were compared. The phosphodiesterase expression profile was also analyzed for peripheral blood monocytes, T lymphocytes, and neutrophils from nonsmokers and compared with smokers. Qualitative RT-PCR identified transcripts for PDE4A10, PDE4A7, PDE4B1, PDE4B2, PDE4D1, and PDE4D2 isoforms as well as transcripts for both PDE3B and PDE7A in T cells, monocytes, and macrophages in all subjects. Transcripts for PDE4B3 and PDE4D4 were not observed in any of the cell types investigated. PDE4C was detected in all cells analyzed except for T cells. The long PDE4A4, PDE4D3, and PDE4D5 isoforms exhibited cell type-specific expression patterns. Semiquantitative and real-time quantitative RT-PCR were used to analyze differential expression between disease states and between cell types. PDE4A4 was found significantly upregulated in lung macrophages from smokers with COPD when compared with control smokers. Furthermore, PDE4A4 as well as PDE4B2 transcripts were detected in higher amounts in peripheral blood monocytes of smokers when compared with nonsmokers. Finally, PDE4D5 and PDE4C were differentially regulated in lung macrophages when compared with monocytes of the same subjects, irrespective of the disease state. The data obtained suggest that PDE4A4 may be relevant as a macrophage-specific anti-inflammatory target for COPD.