High MMP-9 activity characterises pleural tuberculosis correlating with granuloma formation.
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 x mL(-1) versus 43 (12-83) pg x 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.
Sheen
P
P
Department of Microbiology, Universidad Peruana Cayetano Heredia, Lima, Peru.
O'Kane
C M
CM
Chaudhary
K
K
Tovar
M
M
Santillan
C
C
Sosa
J
J
Caviedes
L
L
Gilman
R H
RH
Stamp
G
G
Friedland
J S
JS
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D015769:Granuloma, Respiratory Tract / Q000201:enzymology / Q000209:etiology* / Q000473:pathology; D006801:Humans; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008875:Middle Aged; D010996:Pleural Effusion / Q000201:enzymology / Q000209:etiology / Q000473:pathology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism; D014396:Tuberculosis, Pleural / Q000150:complications / Q000201:enzymology* / Q000473:pathology*
D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1