Human Pleural Effusions Are Rich in Matrix Metalloproteinases

Hurewitz, Adam N.; Zucker, Stanley; Mancuso, Paul; Wu, Chien Liang; Dimassimo, Betty; Lysik, Rita M.; Moutsiakis, Demetrius

doi:10.1378/chest.102.6.1808

Cited by 38 publications

(23 citation statements)

References 17 publications

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“…MMPs, together with TIMPs, have been suggested to play a role in the pathogenesis of pleural effusions, as in many other disease processes [6, 7, 31]. There have been a few reports concerning MMPs and TIMPs in pleural effusions, one of which reported higher concentrations of MMP-9 in tuberculous pleural effusions than in transudates [14].…”

Section: Discussionmentioning

confidence: 99%

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Expression of Matrix Metalloproteinase-9 in Pleural Effusions of Tuberculosis and Lung Cancer

et al. 2005

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Background: Matrix metalloproteinase (MMP)-9 has been implicated in the development of pleural effusions. Objectives: The aim of this study was to assess the expression of MMP-9 in pleural effusions of tuberculosis, lung cancer and transudates. Methods: Ninety-one patients (37 tuberculous pleural effusions, 42 malignant pleural effusions of lung cancer and 12 transudates) were included. Concentrations of pleural fluid MMP-9 and tissue inhibitors of matrix metalloproteinase (TIMP)-1 were determined by immunoassay. We also investigated the cellular localization of MMP-9 and TIMP-1 by reverse-transcriptase polymerase chain reaction on lymphocytes from pleural effusions and by immunohistochemical analysis of pleural tissues. Results: Pleural fluid MMP-9 levels, MMP-9/total protein and MMP-9/TIMP-1 ratios were significantly higher in tuberculous pleural effusions, whilst TIMP-1 levels were similar in the three groups. MMP-9 levels positively correlated with TIMP-1 and lactate dehydrogenase levels, and negatively with pH and glucose levels in pleural effusions. MMP-9 mRNA expression in lymphocytes tended to be higher in malignant pleural effusions of lung cancer than in the other groups without reaching statistical significance. The strongest immunoreactivity for MMP-9 was observed in epithelioid cells of tuberculous pleural tissues. Much lower levels of MMP-9 expression were found in tumor cells of pleural tissues. Conclusions: MMP-9 is increased in tuberculous pleural effusions compared with transudates and malignant pleural effusions of lung cancer and is produced predominantly by epithelioid cells in the granulomas of tuberculous pleural tissues.

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Section: Discussionmentioning

confidence: 99%

“…Proteolytic processes may play a role in the formation of pleural effusions by increasing vascular permeability, and therefore by facilitating fluid influx into the pleural space [5]. The presence and enzymatic activities of MMPs and TIMPs have been identified in pleural effusions [6, 7]. …”

Section: Introductionmentioning

confidence: 99%

Expression of Matrix Metalloproteinase-9 in Pleural Effusions of Tuberculosis and Lung Cancer

et al. 2005

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“…The authors of two previous reports did not find significant differences in the levels of MMP-1, MMP-2 and TIMP-1 in several types of pleural fluids [1,2]. Thus, they considered their expression in pleural fluid to be a constitutive characteristic of the resident mesothelial cells [1,2].…”

Section: Mmps and Timps In Pleural Effusionmentioning

confidence: 93%

“…P roteolytic enzymes that are responsible for breakdown of the extracellular matrix play an important role in inflammatory processes, although they have been hardly studied in relation to the pathogenesis of exudative pleural effusions [1,2]. The metalloproteinases (MMPs) are a family of proteases containing ¢21 members that break down virtually all the protein components of the extracellular matrix.…”

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confidence: 99%

Metalloproteinases and tissue inhibitors of metalloproteinases in exudative pleural effusions

Iglesias¹

2005

Eur Respir J

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The aim of this study was to assess the expression of several metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in exudative pleural effusions, and their relationship with inflammatory and fibrinolytic mediators in parapneumonic effusions.The study included 51 parapneumonic effusions (30 empyema or complicated parapneumonic, 21 noncomplicated parapneumonic), 28 tuberculous, 30 malignant and 30 transudates. Inflammatory markers (tumour necrosis factor-a, interleukin-8, polymorphonuclear elastase), fibrinolytic system variables (tissue plasminogen activator (PA), urokinase PA (u-PA), plasminogen activation inhibitor (PAI)-1, PAI-2), and several MMPs (MMP-1, MMP-2, MMP-8, MMP-9) and TIMPs (TIMP-1, TIMP-2) were determined by ELISA in plasma and pleural fluid.Elevated MMP-2 and TIMP-1 concentrations were observed in all the pleural fluid samples studied. The group of empyema or complicated parapneumonic effusions showed higher MMP-1, MMP-8 and MMP-9 concentrations than the remaining exudates. There was no correlation between MMP and TIMP levels in plasma and pleural fluid in this group of effusions. In parapneumonic effusions, MMP-1, MMP-8 and MMP-9 showed a positive correlation with the inflammatory markers and with u-PA and PAI-1. Moreover, there was a relationship between MMP-8 concentration in pleural fluid and pleural thickening at the end of treatment.In conclusion, elevated metalloproteinase-1, -8 and -9 expression was found in parapneumonic pleural effusions. These metalloproteinases could be implicated in the local inflammatory response existing in this group of effusions.

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“…A further group of 10 patients with pleural effusions due to metastatic carcinoma served as a positive control for the analysis of MMP expression. Pleural effusions due to metastatic carcinoma are associated with high MMP-2 and -9 expression [26]. Ethical approval for the study was from the Institutional Review Boards of Johns Hopkins School of Public Health (Baltimore, MD, USA) and A.B.…”

Section: Stratificationmentioning

confidence: 99%

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

Sheen¹,

O'Kane²,

Chaudhary³

et al. 2008

Eur Respir J

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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.

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Human Pleural Effusions Are Rich in Matrix Metalloproteinases

Cited by 38 publications

References 17 publications

Expression of Matrix Metalloproteinase-9 in Pleural Effusions of Tuberculosis and Lung Cancer

Expression of Matrix Metalloproteinase-9 in Pleural Effusions of Tuberculosis and Lung Cancer

Metalloproteinases and tissue inhibitors of metalloproteinases in exudative pleural effusions

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

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