Skip to main content
Erschienen in: Lung 6/2016

27.09.2016

Profile of Metalloproteinases and Their Association with Inflammatory Markers in Pleural Effusions

verfasst von: Lisete Ribeiro Teixeira, Murilo B. Dias, Roberta K. B. Sales, Leila Antonangelo, Vanessa A. Alvarenga, Juliana Puka, Evaldo Marchi, Milena Marques Pagliarelli Acencio

Erschienen in: Lung | Ausgabe 6/2016

Einloggen, um Zugang zu erhalten

Abstract

Background

Matrix metalloproteinases (MMPs) are responsible for the breakdown of the extracellular matrix and play an important role in the inflammatory processes of pleural exudates. The imbalance between MMPs and their inhibitors (TIMPs) is present in various pathological processes.

Objective

To evaluate the profile of MMPs and TIMPs in pleural effusions of different etiologies correlated with inflammatory markers.

Methods

The patients with pleural effusion due to tuberculosis (TB), cancer (CA) or transudate were prospectively evaluated. Pleural fluid was submitted to cytological, biochemical, cytokines, MMP, and TIMP analysis. Statistical analysis was performed using ANOVA and Spearman’s correlation, and p < 0.05 was considered significant.

Results

One hundred and fourteen patients were enrolled, 80 exudates (41 TB and 39 CA) and 34 transudates. The levels of MMP-8 and MMP-9 were higher in exudates compared to transudates. The level of MMP-8 was significantly higher in TB than in CA. TIMP-1 levels were higher in exudates. IL-6, VEGF, and TGF-β1 showed differences between exudates and transudates. However, IL-6 level was higher in TB than in CA. We found a significant correlation between MMPs and TIMPs with inflammation markers. MMP-1 was correlated with LDH levels. MMP-8 was correlated with LDH, total cell count, neutrophils, and ADA as well as MMP-1 levels. MMP-9 was correlated with IL-6, TGF-β1, and VEGF. TIMP-1 was correlated with MMP-9 and IL-6.

Conclusions

MMPs and TIMPs are expressed in pleural fluid of different etiologies and correlate with inflammatory mediators. MMPs may be useful in determining the cause of fluid, but more studies are needed to determine the spectrum of diseases associated with the various isoforms of MMPS and TIMPs.
Literatur
1.
Zurück zum Zitat Light RW, Mac Gregor MI, Luchsinger PC et al (1972) Pleural effusions: the diagnostic separation of transudates and exudates. Ann Intern Med 77:507–513CrossRefPubMed Light RW, Mac Gregor MI, Luchsinger PC et al (1972) Pleural effusions: the diagnostic separation of transudates and exudates. Ann Intern Med 77:507–513CrossRefPubMed
2.
Zurück zum Zitat Philip-Joét F, Alessi MC, Philip-Joét C et al (1995) Fibrinolytic and inflammatory processes in pleural effusions. Eur Respir J 8:1352–1356CrossRefPubMed Philip-Joét F, Alessi MC, Philip-Joét C et al (1995) Fibrinolytic and inflammatory processes in pleural effusions. Eur Respir J 8:1352–1356CrossRefPubMed
3.
Zurück zum Zitat Antony VB, Godbey SW, Kunkel SL et al (1993) Recruitment of inflammatory cells to the pleural space. J Immunol 151:7216–7223PubMed Antony VB, Godbey SW, Kunkel SL et al (1993) Recruitment of inflammatory cells to the pleural space. J Immunol 151:7216–7223PubMed
4.
Zurück zum Zitat Hurewitz AN, Zucker S, Mancuso P et al (1992) Human pleural effusions are rich in matrix metalloproteinases. Chest 102:1808–1814CrossRefPubMed Hurewitz AN, Zucker S, Mancuso P et al (1992) Human pleural effusions are rich in matrix metalloproteinases. Chest 102:1808–1814CrossRefPubMed
5.
Zurück zum Zitat Eickelberg O, Sommerfeld CO, Wyser C et al (1997) MMP and TIMP expression pattern in pleural effusions of different origins. Am J Respir Crit Care Med 156:1987–1992CrossRefPubMed Eickelberg O, Sommerfeld CO, Wyser C et al (1997) MMP and TIMP expression pattern in pleural effusions of different origins. Am J Respir Crit Care Med 156:1987–1992CrossRefPubMed
6.
Zurück zum Zitat Pritchard SC, Nicolson MC, Lloret C et al (2001) Expression of matrix metalloproteinases 1, 2, 9 and their tissue inhibitors in stage II non-small cell lung cancer: implications for MMp inhibition therapy. Oncol Rep 8:421–428PubMed Pritchard SC, Nicolson MC, Lloret C et al (2001) Expression of matrix metalloproteinases 1, 2, 9 and their tissue inhibitors in stage II non-small cell lung cancer: implications for MMp inhibition therapy. Oncol Rep 8:421–428PubMed
7.
Zurück zum Zitat D´Agostino P, Cameni AR, Caruso R et al (2003) Matrix metalloproteinase production in malignant pleural effusions after talc pleurodesis. Clin Exp Immunol 134:138–142CrossRef D´Agostino P, Cameni AR, Caruso R et al (2003) Matrix metalloproteinase production in malignant pleural effusions after talc pleurodesis. Clin Exp Immunol 134:138–142CrossRef
8.
Zurück zum Zitat Woessner JF Jr (1991) Matrix metalloproteinases and their inhibitors in connective tissue remodeling. FASEB J 5:2145–2154PubMed Woessner JF Jr (1991) Matrix metalloproteinases and their inhibitors in connective tissue remodeling. FASEB J 5:2145–2154PubMed
9.
Zurück zum Zitat Birkedal-Hansen H, Moore WG, Bodden MK et al (1993) Matrix metalloproteinases: a review. Crit Rev Oral Biol Med 4:197–250PubMed Birkedal-Hansen H, Moore WG, Bodden MK et al (1993) Matrix metalloproteinases: a review. Crit Rev Oral Biol Med 4:197–250PubMed
10.
Zurück zum Zitat Murphy G, Docherty AJP (1992) The matrix metalloproteinases and their inhibitors. Am J Respir Cell Mol Biol 7:120–125CrossRefPubMed Murphy G, Docherty AJP (1992) The matrix metalloproteinases and their inhibitors. Am J Respir Cell Mol Biol 7:120–125CrossRefPubMed
11.
Zurück zum Zitat Ma C, Tarnuzzer RW, Chengini N (1999) Expression of matrix metalloproteinases in tissue inhibitor of matrix metalloproteinases in mesothelial cells and their regulation by transforming growth factor-β1. Wound Repair Reqagen 7:477–485CrossRef Ma C, Tarnuzzer RW, Chengini N (1999) Expression of matrix metalloproteinases in tissue inhibitor of matrix metalloproteinases in mesothelial cells and their regulation by transforming growth factor-β1. Wound Repair Reqagen 7:477–485CrossRef
12.
Zurück zum Zitat Opdenakker G, Van den Steen PE, Van Damme J (2001) Gelatinase B: a tuner and amplifier of immune functions. Trends Immunol 22:571–579CrossRefPubMed Opdenakker G, Van den Steen PE, Van Damme J (2001) Gelatinase B: a tuner and amplifier of immune functions. Trends Immunol 22:571–579CrossRefPubMed
13.
Zurück zum Zitat Gomez DE, Alonso DF, Yoshiji H et al (1997) Tissue inhibitors of metalloproteinases: structure, function and biological functions. Eur J Cell Biol 74:111–122PubMed Gomez DE, Alonso DF, Yoshiji H et al (1997) Tissue inhibitors of metalloproteinases: structure, function and biological functions. Eur J Cell Biol 74:111–122PubMed
14.
Zurück zum Zitat Ray JM, Stetler-Stevenson WG (1994) The role of matrix metalloproteinases and their inhibitors in tumor invasion, metastasis and angiogenesis. Eur Respir J 7:2062–2072PubMed Ray JM, Stetler-Stevenson WG (1994) The role of matrix metalloproteinases and their inhibitors in tumor invasion, metastasis and angiogenesis. Eur Respir J 7:2062–2072PubMed
15.
Zurück zum Zitat Pugin J, Widmer M-C, Kossodo S et al (1999) Human neutrophils secrete gelatinase B in vitro and in vivo in response to endotoxin and proinflammatory mediators. Am J Respir Cell Mol Biol 20:458–464CrossRefPubMed Pugin J, Widmer M-C, Kossodo S et al (1999) Human neutrophils secrete gelatinase B in vitro and in vivo in response to endotoxin and proinflammatory mediators. Am J Respir Cell Mol Biol 20:458–464CrossRefPubMed
16.
Zurück zum Zitat Leppert D, Leib SL, Grygar C et al (2000) Matrix metalloproteinase (MMP)-8 and MMP-9 in cerebrospinal fluid during bacterial meningitis: association with bloodbrain barrier damage and neurological sequelae. Clin Infect Dis 31:80–84CrossRefPubMed Leppert D, Leib SL, Grygar C et al (2000) Matrix metalloproteinase (MMP)-8 and MMP-9 in cerebrospinal fluid during bacterial meningitis: association with bloodbrain barrier damage and neurological sequelae. Clin Infect Dis 31:80–84CrossRefPubMed
17.
Zurück zum Zitat Sheen P, O´Kane CM, Chaudhary K et al (2009) High MMP-9 activity characterises pleural tuberculosis correlating with granuloma formation. Eur Respir J 33:134–141CrossRefPubMed Sheen P, O´Kane CM, Chaudhary K et al (2009) High MMP-9 activity characterises pleural tuberculosis correlating with granuloma formation. Eur Respir J 33:134–141CrossRefPubMed
18.
Zurück zum Zitat Lijnen HR (2001) Plasmin and matrix metalloproteinases in vascular remodelling. Thromb Haemost 86:324–333PubMed Lijnen HR (2001) Plasmin and matrix metalloproteinases in vascular remodelling. Thromb Haemost 86:324–333PubMed
19.
Zurück zum Zitat Antony VB, Mohammed KA (1999) Pathophysiology of pleural space infections. Semin Respir Infect 14:9–17PubMed Antony VB, Mohammed KA (1999) Pathophysiology of pleural space infections. Semin Respir Infect 14:9–17PubMed
20.
Zurück zum Zitat Streeter RM, Lukacs NW, Standiford TJ et al (1993) Cytokines and lung inflammation mechanisms of neutrophils recruitment to the lung. Thorax 48:765–769CrossRef Streeter RM, Lukacs NW, Standiford TJ et al (1993) Cytokines and lung inflammation mechanisms of neutrophils recruitment to the lung. Thorax 48:765–769CrossRef
21.
Zurück zum Zitat Fujino S, Yokoyama A, Kohno N et al (1996) Interleukin 6 is an autocrine growth factor for normal human pleural mesothelial cells. Am J Respir Cell Mol Biol 14:508–515CrossRefPubMed Fujino S, Yokoyama A, Kohno N et al (1996) Interleukin 6 is an autocrine growth factor for normal human pleural mesothelial cells. Am J Respir Cell Mol Biol 14:508–515CrossRefPubMed
22.
Zurück zum Zitat Hoeben A, Landuyt B, Highley MS et al (2004) Vascular endothelial growth factor and angiogenesis. Pharmacol Rev 56:549–580CrossRefPubMed Hoeben A, Landuyt B, Highley MS et al (2004) Vascular endothelial growth factor and angiogenesis. Pharmacol Rev 56:549–580CrossRefPubMed
23.
Zurück zum Zitat Fiorelli A, Vicidomini G, Di Domenico M et al (2011) Vascular endothelial growth factor in pleural fluid for differential diagnosis of benign and malignant origin and its clinical applications. Interact Cardiovasc Thorac Surg 12:420–424CrossRefPubMed Fiorelli A, Vicidomini G, Di Domenico M et al (2011) Vascular endothelial growth factor in pleural fluid for differential diagnosis of benign and malignant origin and its clinical applications. Interact Cardiovasc Thorac Surg 12:420–424CrossRefPubMed
24.
Zurück zum Zitat Sack U, Hoffmann M, Zhao XJ et al (2005) Vascular endothelial growth factor in pleural effusions of different origin. Eur Respir J 25:600–604CrossRefPubMed Sack U, Hoffmann M, Zhao XJ et al (2005) Vascular endothelial growth factor in pleural effusions of different origin. Eur Respir J 25:600–604CrossRefPubMed
25.
Zurück zum Zitat Seiscento M, Vargas FS, Antonangelo L et al (2007) Transforming growth factor beta-1 as a predictor of fibrosis in tuberculous pleurisy. Respirology 12:660–663CrossRefPubMed Seiscento M, Vargas FS, Antonangelo L et al (2007) Transforming growth factor beta-1 as a predictor of fibrosis in tuberculous pleurisy. Respirology 12:660–663CrossRefPubMed
26.
Zurück zum Zitat Sundararajan S, Babu S, Das SD (2012) Comparison of localized versus systemic levels of matrix metalloproteinases (MMPs), its tissue inhibitors (TIMPs) and cytokines in tuberculous and non tuberculous pleuritis patients. Hum Immunol 73:985–991CrossRefPubMedPubMedCentral Sundararajan S, Babu S, Das SD (2012) Comparison of localized versus systemic levels of matrix metalloproteinases (MMPs), its tissue inhibitors (TIMPs) and cytokines in tuberculous and non tuberculous pleuritis patients. Hum Immunol 73:985–991CrossRefPubMedPubMedCentral
27.
Zurück zum Zitat Sepper R, Konttinen YT, Ding Y et al (1995) Human neophils collagenase (MMP-8), identified in bronchiectasis BAL fluid, correlates with severity of disease. Chest 107:1641–1647CrossRefPubMed Sepper R, Konttinen YT, Ding Y et al (1995) Human neophils collagenase (MMP-8), identified in bronchiectasis BAL fluid, correlates with severity of disease. Chest 107:1641–1647CrossRefPubMed
28.
Zurück zum Zitat Finlay GA, Russel KJ, McMahon H et al (1996) Matrix metalloproteinases in emphysema. Thorax 51:A51CrossRef Finlay GA, Russel KJ, McMahon H et al (1996) Matrix metalloproteinases in emphysema. Thorax 51:A51CrossRef
29.
Zurück zum Zitat Delacourt CM, Le Bourgeois M, d´Ortho MP et al (1995) Imbalance between 95 kDa type IV collagenase and tissue inhibitor of metalloproteinases in sptum of patients with cystic fibrosis. Am J Respir Crit Care Med 152:765–774CrossRefPubMed Delacourt CM, Le Bourgeois M, d´Ortho MP et al (1995) Imbalance between 95 kDa type IV collagenase and tissue inhibitor of metalloproteinases in sptum of patients with cystic fibrosis. Am J Respir Crit Care Med 152:765–774CrossRefPubMed
30.
Zurück zum Zitat Quiding-Jarbrink M, Smith DA, Bancroft GJ (2001) Production of matrix metalloproteinases in response to mycobacterial infection. Infect Immunol 69:5661–5670CrossRef Quiding-Jarbrink M, Smith DA, Bancroft GJ (2001) Production of matrix metalloproteinases in response to mycobacterial infection. Infect Immunol 69:5661–5670CrossRef
31.
Zurück zum Zitat Price NM, Farrar J, Tran TT et al (2001) Identification of matrix-degrading phenotype in human tuberculosis in vitro and in vivo. J Immunol 166:4223–4230CrossRefPubMed Price NM, Farrar J, Tran TT et al (2001) Identification of matrix-degrading phenotype in human tuberculosis in vitro and in vivo. J Immunol 166:4223–4230CrossRefPubMed
32.
Zurück zum Zitat Jiang Y, Wang M, Celiker M et al (2001) Stimulation of mammary tumorigenesis y systemic inhibitor of matrix metalloproteinase 4 gene delivery. Cancer Res 61:2365–2370PubMed Jiang Y, Wang M, Celiker M et al (2001) Stimulation of mammary tumorigenesis y systemic inhibitor of matrix metalloproteinase 4 gene delivery. Cancer Res 61:2365–2370PubMed
33.
Zurück zum Zitat Baker AH, George SJ, Zaltsman AB et al (1999) Inhibition of invasion and induction of apoptotic cell death of cancer cell lines by overexpression of TIMP-3. Br J Cancer 79:1347–1355CrossRefPubMedPubMedCentral Baker AH, George SJ, Zaltsman AB et al (1999) Inhibition of invasion and induction of apoptotic cell death of cancer cell lines by overexpression of TIMP-3. Br J Cancer 79:1347–1355CrossRefPubMedPubMedCentral
34.
Zurück zum Zitat Iglesias D, Alegre J, Aleman C et al (2005) Metalloproteinases and tissue inhibitors of metalloproteinases in exudative pleural effusion. Eur Respir J 25:104–109CrossRefPubMed Iglesias D, Alegre J, Aleman C et al (2005) Metalloproteinases and tissue inhibitors of metalloproteinases in exudative pleural effusion. Eur Respir J 25:104–109CrossRefPubMed
35.
Zurück zum Zitat Saren P, Welgus HG, Kovanen PT (1996) TNF-alpha and IL-1 beta selectively induce expression of 92-kDa gelatinase by human macrophages. J Immunol 157:4159–4165PubMed Saren P, Welgus HG, Kovanen PT (1996) TNF-alpha and IL-1 beta selectively induce expression of 92-kDa gelatinase by human macrophages. J Immunol 157:4159–4165PubMed
36.
Zurück zum Zitat Fiorelli A, Morgillo F, Fasano M et al (2013) The value of matrix metalloproteinase-9 and vascular endothelial growth factor receptor 1 pathway in diagnosing indeterminate pleural effusion. Interact Cardiovasc Thorac Surg 16:263–269CrossRefPubMed Fiorelli A, Morgillo F, Fasano M et al (2013) The value of matrix metalloproteinase-9 and vascular endothelial growth factor receptor 1 pathway in diagnosing indeterminate pleural effusion. Interact Cardiovasc Thorac Surg 16:263–269CrossRefPubMed
Metadaten
Titel
Profile of Metalloproteinases and Their Association with Inflammatory Markers in Pleural Effusions
verfasst von
Lisete Ribeiro Teixeira
Murilo B. Dias
Roberta K. B. Sales
Leila Antonangelo
Vanessa A. Alvarenga
Juliana Puka
Evaldo Marchi
Milena Marques Pagliarelli Acencio
Publikationsdatum
27.09.2016
Verlag
Springer US
Erschienen in
Lung / Ausgabe 6/2016
Print ISSN: 0341-2040
Elektronische ISSN: 1432-1750
DOI
https://doi.org/10.1007/s00408-016-9945-5

Weitere Artikel der Ausgabe 6/2016

Lung 6/2016 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.