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Am J Physiol Lung Cell Mol Physiol (October 4, 2002). doi:10.1152/ajplung.00170.2002
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Articles in PresS, published online ahead of print October 4, 2002
Am J Physiol Lung Cell Mol Physiol, 10.1152/ajplung.00170.2002
Submitted on June 3, 2002
Accepted on September 26, 2002

Ubiquitous Expression of Phosphodiesterase 7A in Human Pro-inflammatory and Immune Cells

Susan J. Smith1, Steven Brookes-Fazakerley1, Louise E. Donnelly1, Peter J. Barnes1, Mary S. Barnette2, and Mark A. Giembycz1*

1 Thoracic Medicine, National Heart & Lung Institute, Imperial College of Science, Technology and Medicine, London, United Kingdom
2 Department of Pulmonary Pharmacology, GlaxoSmithKline, Philadelphia, PA, USA

* To whom correspondence should be addressed. E-mail: m.giembycz{at}ic.ac.uk.

We have determined the expression of PDE7A1 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 and 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.




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