Lung transplant metalloproteinase levels are elevated prior to bronchiolitis obliterans syndrome

G. N. Smith, E. A. Mickler, K. K. Payne, J. Lee, M. Duncan, J. Reynolds, B. Foresman, D. S. Wilkes

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

Parenchymal disease in the allograft lung is associated with interstitial remodeling believed to be mediated by matrix metalloproteinases (MMPs). Recent studies suggest high levels of MMP-9 are associated with bronchiolitis obliterans syndrome (BOS) in lung transplant recipients. Since BOS occurs late in the posttransplant period and may be preceded by episodes of acute rejection or infection, which are associated with interstitial remodeling, we examined MMP profiles in allograft bronchoalveolar lavage (BAL) fluid in the early posttransplant period (preceding BOS). Gelatin zymography, protein array analysis and specific ELISA on BAL fluids from transplanted lungs indicated that MMP-8, MMP-9 and TIMP-1 were strongly expressed in allograft BAL fluid from stable patients, or those with infection or rejection compared to BAL fluid from normal volunteers. Elevated expression of MMP-8, MMP-9 and TIMP-1 occurred early, and was sustained for the 3.2 years covered in this study. Elevations of MMP-8, MMP-9 and TIMP-1 in the first 2 years posttransplant appear to be associated with lung transplantation itself, and not infection or rejection. These data suggest that ongoing and clinically silent MMP activity could perpetuate progressive disease in the allograft lung.

Original languageEnglish (US)
Pages (from-to)1856-1861
Number of pages6
JournalAmerican Journal of Transplantation
Volume7
Issue number7
DOIs
StatePublished - Jul 2007

Keywords

  • BOS
  • Collagen
  • Lung transplantation
  • MMP
  • TIMP

ASJC Scopus subject areas

  • Immunology

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    Smith, G. N., Mickler, E. A., Payne, K. K., Lee, J., Duncan, M., Reynolds, J., Foresman, B., & Wilkes, D. S. (2007). Lung transplant metalloproteinase levels are elevated prior to bronchiolitis obliterans syndrome. American Journal of Transplantation, 7(7), 1856-1861. https://doi.org/10.1111/j.1600-6143.2007.01850.x