Emphysema mediated by lung overexpression of ADAM10.

Hiroki Saitoh, Philip L. Leopold, Ben Gary Harvey, Timothy P. O'Connor, Stefan Worgall, Neil R. Hackett, Ronald G. Crystal

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Abstract

Cigarette smoking is the major risk factor for emphysema, a disorder of the lung parenchyma characterized by destruction of the alveolar walls. Current concepts of the pathogenesis of emphysema hold that the destruction of the lung parenchyma results, in part, from a local imbalance of proteases and antiproteases. Based on the knowledge that human alveolar macrophages express ADAM 10, a protease capable of destroying basement membrane collagen but not previously implicated in emphysema, we used adenovirus-mediated lung expression of ADAM 10 in a mouse model to assess whether an increased burden of ADAM 10 was capable of inducing emphysema. To assess this, the human ADAM 10 cDNA under control of a constitutive promoter was inserted into an adenovirus gene transfer vector (AdhADAMlO), and the vector (10(11) particle units) administered to the respiratory tract of wild type C57BI/6 mice. Lung levels of ADAM 10 mRNA and protein were upregulated following AdhADAMlO administration. After 8 weeks, quantitative morphometry of the lung parenchyma demonstrated that AdhADAMlO administration induced emphysema (mean linear intercept of 60.6 + 1.3 microm compared with 55.6 + 0.8 in mice treated with a control vector, p < 0.003). These results suggest a role of ADAM 10 in the pathogenesis of emphysema, adding to the list of proteases expressed in the lung that are capable of contributing to the development of lung destruction.

Original languageEnglish
Pages (from-to)50-56
Number of pages7
JournalClinical and translational science
Volume2
Issue number1
DOIs
Publication statusPublished - Feb 2009

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ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Saitoh, H., Leopold, P. L., Harvey, B. G., O'Connor, T. P., Worgall, S., Hackett, N. R., & Crystal, R. G. (2009). Emphysema mediated by lung overexpression of ADAM10. Clinical and translational science, 2(1), 50-56. https://doi.org/10.1111/j.1752-8062.2008.00085.x