Barber Rachael, Baillie George S, Bergmann Reinhard, Shepherd Malcolm C, Sepper Ruth, Houslay Miles D, Heeke Gino Van
Respiratory Disease Area, Novartis Horsham Research Center, Wimblehurst Road, Horsham RH12 5AB, United Kingdom.
Am J Physiol Lung Cell Mol Physiol. 2004 Aug;287(2):L332-43. doi: 10.1152/ajplung.00384.2003. Epub 2004 Mar 26.
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.
测定了与慢性阻塞性肺疾病（COPD）相关的一组15种环磷酸腺苷磷酸二酯酶同工型在炎症细胞类型中的表达谱。特别比较了患有和未患有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。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。定性逆转录聚合酶链反应（RT-PCR）鉴定出所有受试者的T细胞、单核细胞和巨噬细胞中PDE4A10、PDE4A7、PDE4B1、PDE4B2、PDE4D1和PDE4D2同工型的转录本以及PDE3B和PDE7A的转录本。在所研究的任何细胞类型中均未观察到PDE4B3和PDE4D4的转录本。除T细胞外，在所有分析的细胞中均检测到PDE4C。长链PDE4A4、PDE4D3和PDE4D5同工型表现出细胞类型特异性的表达模式。使用半定量和实时定量RT-PCR分析疾病状态之间以及细胞类型之间的差异表达。与对照吸烟者相比，发现患有COPD的吸烟者肺巨噬细胞中PDE4A4显著上调。此外，与非吸烟者相比，吸烟者外周血单核细胞中检测到的PDE4A4以及PDE4B2转录本含量更高。最后，与同一受试者的单核细胞相比，无论疾病状态如何，肺巨噬细胞中PDE4D5和PDE4C的表达受到不同调节。所获得的数据表明，PDE4A4可能作为COPD巨噬细胞特异性抗炎靶点具有相关性。
