Interferon γ induction of pulmonary emphysema in the adult murine lung

Zhongde Wang, Tao Zheng, Zhou Zhu, Robert J. Homer, Richard J. Riese, Harold A. Chapman, Steven D. Shapiro, Jack A. Elias

Research output: Contribution to journalArticle

Abstract

Chronic inflammation containing CD8+ lymphocytes, neutrophils, and macrophages, and pulmonary emphysema coexist in lungs from patients with chronic obstructive pulmonary disease. Although this inflammatory response is believed to cause the remodeling that is seen in these tissues, the mechanism(s) by which inflammation causes emphysema have not been defined. Here we demonstrate that interferon γ (IFN-γ), a prominent product of CD8+ cells, causes emphysema with alveolar enlargement, enhanced lung volumes, enhanced pulmonary compliance, and macrophage- and neutrophil-rich inflammation when inducibly targeted, in a transgenic fashion, to the adult murine lung. Prominent protease and antiprotease alterations were also noted in these mice. They included the induction and activation of matrix metalloproteinase (MMP)-12 and cathepsins B, H, D, S, and L, the elaboration of MMP-9, and the selective inhibition of secretory leukocyte proteinase inhibitor. IFN-γ causes emphysema and alterations in pulmonary protease/antiprotease balance when expressed in pulmonary tissues.

Original languageEnglish (US)
Pages (from-to)1587-1599
Number of pages13
JournalJournal of Experimental Medicine
Volume192
Issue number11
DOIs
StatePublished - Dec 4 2000

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Keywords

  • Cathepsin
  • Chronic obstructive pulmonary disease
  • Matrix metalloproteinase
  • Neutrophil
  • Secretory leukocyte proteinase inhibitor

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Wang, Z., Zheng, T., Zhu, Z., Homer, R. J., Riese, R. J., Chapman, H. A., Shapiro, S. D., & Elias, J. A. (2000). Interferon γ induction of pulmonary emphysema in the adult murine lung. Journal of Experimental Medicine, 192(11), 1587-1599. https://doi.org/10.1084/jem.192.11.1587