Ubiquitous expression of phosphodiesterase 7A in human proinflammatory and immune cells.
We have determined the expression of phosphodiesterase (PDE) 7A1 and PDE7A2 in human cells that have been implicated in the pathogenesis of chronic obstructive pulmonary disease and asthma. Messenger RNA transcripts were detected by RT-PCR in T lymphocytes, monocytes, neutrophils, airway and vascular smooth muscle cells, lung fibroblasts, epithelial cells, and cardiac myocytes. Human epithelial, T cell, eosinophil, and lung fibroblast cell lines were also positive for PDE7A1 and PDE7A2 mRNA transcripts. By Western immunoblot analyses the amount of PDE7A1 was greatest in T cell lines, peripheral blood T lymphocytes, epithelial cell lines, airway and vascular smooth muscle cells, lung fibroblasts, and eosinophils but was not detected in neutrophils. In contrast, PDE7A2 protein, which was identified in human cardiac myocytes, was not found in any of the other cell types investigated. Immunoconfocal analyses showed that PDE7A was expressed in neutrophils and alveolar macrophages. As the expression of PDE7A mirrors the distribution of PDE4 we speculate that this enzyme could be a target for novel anti-inflammatory drugs.
Smith
Susan J
SJ
Thoracic Medicine, National Heart and Lung Institute, Faculty of Medicine, Imperial College of Science, Technology and Medicine, London SW3 6LY, United Kingdom.
Brookes-Fazakerley
Steven
S
Donnelly
Louise E
LE
Barnes
Peter J
PJ
Barnette
Mary S
MS
Giembycz
Mark A
MA
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D015153:Blotting, Western; D002478:Cells, Cultured; D054708:Cyclic Nucleotide Phosphodiesterases, Type 7; D006801:Humans; D007107:Immune System / Q000166:cytology; D007150:Immunohistochemistry; D007249:Inflammation / Q000209:etiology; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000201:enzymology*; D018613:Microscopy, Confocal; D009504:Neutrophils / Q000201:enzymology* / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D014018:Tissue Distribution
D007527:Isoenzymes; D012333:RNA, Messenger; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054708:Cyclic Nucleotide Phosphodiesterases, Type 7; C517458:PDE7A protein, human