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

¹ Dept of Microbiology, Universidad Peruana Cayetano Heredia, ⁵ Dept of Pulmonology, Dos de Mayo Hospital, Lima, Peru, ² Dept of International Health, Johns Hopkins University, School of Hygiene and Public Health, Baltimore, MD, USA, ³ Dept of Infectious Diseases and Wellcome Trust Centre for Clinical Tropical Medicine, and ⁴ Dept of Pathology, Imperial College London, Hammersmith Campus, London, UK.

CORRESPONDENCE: J. S. Friedland, Dept of Infectious Diseases and Immunity, Faculty of Medicine, Imperial College, Du Cane Rd, Hammersmith Hospital, London, W12 ONN, UK. Fax: 44 2083833394. E-mail: j.friedland{at}imperial.ac.uk

Keywords: Extracellular matrix, human, inflammation, matrix metalloproteinases, pleura, tuberculosis

Received: September 27, 2007
Accepted July 30, 2008

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.