High MMP-9 activity characterises pleural tuberculosis correlating with granuloma formation

P. Sheen, C. M. O'Kane, K. Chaudhary, M. Tovar, C. Santillan, J. Sosa, L. Caviedes, R. H. Gilman, G. Stamp, J. S. Friedland

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Abstract

Tuberculosis (TB) pleural disease is complicated by extensive tissue destruction. Matrix metalloproteinase (MMP)-1 and -9 are implicated in immunopathology of pulmonary and central nervous system TB. There are few data on MMP activity in TB pleurisy. The present study investigated MMP-1, -2 and -9 and their specific inhibitors (tissue inhibitor of metalloproteinase (TIMP)-1 and -2) in tuberculous effusions, and correlated these with clinical and histopathological features. Clinical data, routine blood tests, and pleural fluid/biopsy material were obtained from 89 patients presenting with pleural effusions in a TB-endemic area. MMP-1, -2 and -9 were measured by zymography or western blot, and TIMP-1 and -2 by ELISA. Pleural biopsies were examined microscopically, cultured for acid-alcohol fast bacilli and immunostained for MMP-9. Tuberculous pleural effusions contained the highest concentrations of MMP-9 compared with malignant effusions or heart failure transudates. MMP-9 concentrations were highest in effusions from patients with granulomatous biopsies: median (interquartile range) 108 (61-218) pg·mL-1 versus 43 (12-83) pg·mL-1 in those with nongranulomatous pleural biopsies. MMP-1 and -2 were not upregulated in tuberculous pleural fluid. The ratio of MMP-9:TIMP-1 was significantly higher in TB effusions. Tuberculous pleurisy is characterised by a specific pattern of matrix metalloproteinase-9 upregulation, correlating with the presence of granulomas and suggesting a specific role for matrix metalloproteinase-9 in inflammatory responses in tuberculous pleural disease. Copyright

Original languageEnglish (US)
Pages (from-to)134-141
Number of pages8
JournalEuropean Respiratory Journal
Volume33
Issue number1
DOIs
StatePublished - Jan 1 2009

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Keywords

  • Extracellular matrix
  • Human
  • Inflammation
  • Matrix metalloproteinases
  • Pleura
  • Tuberculosis

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Sheen, P., O'Kane, C. M., Chaudhary, K., Tovar, M., Santillan, C., Sosa, J., Caviedes, L., Gilman, R. H., Stamp, G., & Friedland, J. S. (2009). High MMP-9 activity characterises pleural tuberculosis correlating with granuloma formation. European Respiratory Journal, 33(1), 134-141. https://doi.org/10.1183/09031936.00127807