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

¹ Dept of Microbiology, Universidad Peruana Cayetano Heredia, PO Box 5045, Lima, Peru; and Dept of International Health, Johns Hopkins University, School of Hygiene and Public Health, Baltimore, Maryland 21205, USA
² Dept of Infectious Diseases & Wellcome Trust Centre for Clinical Tropical Medicine
³ Dept of Pathology, Imperial College London, Hammersmith campus, London, England
⁴ Dept of Microbiology, Universidad Peruana Cayetano Heredia, PO Box 5045, Lima, Peru
⁵ Dept of Pulmonology, Dos de Mayo Hospital, Lima, Peru
⁶ Dept of Microbiology, Universidad Peruana Cayetano Heredia, PO Box 5045, Lima, Peru; Dept of International Health, Johns Hopkins University, School of Hygiene and Public Health, Baltimore, Maryland 21205, USA; and Dept of Infectious Diseases & Wellcome Trust Centre for Clinical Tropical Medicine

^* To whom correspondence should be addressed. E-mail: j.friedland{at}imperial.ac.uk.

	Abstract

Tuberculosis (TB) pleural disease is complicated by extensive tissue destruction. Matrix Metalloproteinases (MMPs) -1 and -9 are implicated in immunopathology of pulmonary and CNS TB. There are few data on MMP activity in TB pleurisy. We investigated MMP-1/-2/-9 and their specific inhibitors (TIMPs-1/-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/-9 were measured by zymography or western blot, and TIMPs-1/-2 by ELISA. Pleural biopsies were examined microscopically, cultured for AAFB 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, 108pg·ml^-1 (interquartile range 61–218) vs. 43pg·ml^-1 (12–83) in those with non-granulomatous pleural biopsies (p=0.001). 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 characterized by a specific pattern of MMP-9 upregulation, correlating with the presence of granulomas and suggesting a specific role for MMP-9 in inflammatory responses in tuberculous pleural disease.