Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
JCR Impact Factor (IF) – 2.1 (5-Year IF – 2.0)
Journal Citation Indicator (JCI) (2023) – 0.4
Scopus CiteScore – 3.7 (CiteScore Tracker 3.8)
Index Copernicus  – 171.00; MNiSW – 70 pts

ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
Periodicity – monthly

Download original text (EN)

Advances in Clinical and Experimental Medicine

2009, vol. 18, nr 3, May-June, p. 303–309

Publication type: review article

Language: English

The Role of Metalloproteinases in the Pathogenesis of Chronic Obstructive Pulmonary Disease

Rola metaloproteinaz w patogenezie przewlekłej obturacyjnej choroby płuc

Paweł Piesiak1,, Maria Kraus−Filarska2,, Monika Kosacka1,, Ewa Passowicz−Muszyńska1,

1 Department of Pulmonary Diseases and Pulmonary Neoplasms, Wroclaw Medical University, Poland

2 Department of Internal Medicine and Allergology, Wroclaw Medical University, Poland

Abstract

Chronic obstructive pulmonary disease (COPD) is a tobacco−related lung disease with an excessive and persistent inflammatory response. There is much evidence that the alterations within the extracellular matrix (ECM) evoked by connective tissue cell dysfunctions play a crucial role in the pathogenesis of COPD. Matrix metalloproteinases (MMPs) are believed to play a crucial role in the degradation of almost all extracellular matrix protein components. This effect may be responsible for the complete destruction of the alveolar walls and the formation of abnormal spaces evolving into larger bullae. Tissue inhibitors of metalloproteinases (TIMPs) regulate the synthesis, secretion, and activity of MMPs. The decreased secretion of TIMPs in COPD patients can favor increased elastolysis in the lung. The causes of the imbalance between MMPs and TIMPs in COPD are yet not clear. The development of new COPD therapies directed against specific MMPs and TIMPs should be the target of future research.

Streszczenie

Przewlekła obturacyjna choroba płuc (p.o.ch.p.) jest schorzeniem tytoniozależnym, w którym istotną rolę odgrywają mechanizmy zapalne. Prowadzą między innymi do zmian składu macierzy pozakomórkowej. Kluczową rolę w tym procesie odgrywają metaloproteinazy macierzy (MMPs – matrix metallproteinases). Jest to grupa enzymów powodująca trawienie niemal wszystkich białek macierzy pozakomórkowej, co prowadzi do zniszczenia ścian pęcherzyków płucnych i tworzenia dużych pęcherzy rozedmowych. Tkankowe inhibitory metaloproteinaz (TIMPs – tissue inhibitors of metalloproteinases) regulują syntezę, wydzielanie oraz aktywację MMPs. Zaburzenie równowagi MMPs/TIMPs na korzyść MMPs, obserwowane u chorych na p.o.ch.p., może sprzyjać nasileniu procesów elastolizy w płucach. Czynniki zaburzające homeostazę składników macierzy pozakomórkowej nie są dobrze poznane. Niezbędne są dalsze badania nad nowymi metodami terapii p.o.ch.p. skierowanymi na swoiste białka MMPs i TIMPs.

Key words

chronic obstructive pulmonary disease, extracellular matrix, metalloproteinases, tissue inhibitors of metalloproteinases

Słowa kluczowe

przewlekła obturacyjna choroba płuc, macierz pozakomórkowa, metaloproteinazy, tkankowy inhibitor metaloproteinaz

References (62)

  1. Lopez AD, Murray CC The global burden of disease, 1990–2020. Nat Med 1998, 4, 1241–1243.
  2. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease Updated 2007, http://www.goldcopd.org
  3. Agusti A, MacNee W, Donaldson K, Cosio M: Hypothesis: does COPD have an autoimmune component? Thorax 2003, 58, 832–834.
  4. Vernooy JH, Kucukaycan M, Jacobs JA et al.: Local and systemic inflammation in patients with chronic obstructive pulmonary disease: soluble tumor necrosis factor receptors are increased in sputum. Am J Respir Crit Care Med 2002, 166, 1218–1224.
  5. Ohnishi K, Takagi M, Kurokawa Y, Satomi S, Konttinen YT: Matrix metalloproteinase−mediated extracellular matrix protein degradation in human pulmonary emphysema. Lab Invest 1998, 78, 1077–1087.
  6. Finkelstein R, Fraser RS, Ghezzo H et al.: Alveolar inflammation and its relation to emphysema in smokers. Am J Respir Crit Care Med 1995, 152, 1666–1672.
  7. Barnes PJ, Shapiro SD, Pauwels RA: Chronic obstructive pulmonary disease: molecular and cellular mechanisms. Eur Respir J 2003, 22, 672–688.
  8. Selman M, Cisneros−Lira J, Gaxiola M et al.: Matrix metalloproteinases inhibition attenuates tobacco smokeinduced emphysema in Guinea pigs. Chest 2003, 123, 1633–1641.
  9. Ohnishi K, Takagi M, Kurokawa Y et al.: Matrix metalloproteinase−mediated extracellular matrix protein degradation in human pulmonary emphysema. Lab Invest 1998, 78, 1077–1087.
  10. Betsuyaku T, Nishimura M, Takeyabu K et al.: Neutrophil granule proteins in bronchoalveolar lavage fluid from subjects with subclinical emphysema. Am J Respir Crit Care Med 1999, 159, 1985–1991.
  11. Greenlee KJ, Werb Z, Kheradmand F: Matrix Metalloproteinases in Lung: Multiple, Multifarious, and Multifaceted. Physiol Rev 2007, 87, 69–98.
  12. Shapiro SD, Senior RM: Matrix Metalloproteinases. Matrix Degradation and More. Am J Respir Cell Mol Biol 1999, 20, 1100–1102.
  13. Kraus−Filarska M, Kosińska M, Tomkowicz A: Metalloproteinases and airway remodeling in asthma. Adv Clin Exp Med 2007, 16, 3, 417–423.
  14. Dollery CM, McEwan JR, Henney AM: Matrix metalloproteinases and cardiovascular disease. Circ Res 1995, 77, 863–868.
  15. Giaquinto P, Liurea P, Trojano M: Serum MMP−9/TIMP−1 and MMP−2/TIMP−2 ratios in multiple sclerosis: relationship with different magnetic resonance imaging measures of disease activity during IFN−beta−1a treatment. Multiple Sclerosis 2005, 11, 441–446.
  16. Coussens LM, Fingleton B, Matrisian LM: Matrix metalloproteinase inhibitors and cancer: trials and tribulations. Science 2002, 295, 2387–2392.
  17. Farrelly N, Lee YJ, Oliver J, Dive C, Streuli CH: Extracellular matrix regulates apoptosis in mammary epithelium through a control on insulin signaling. J. Cell Biol 1999, 144, 1337–1347.
  18. Pilcher BK, Dumin JA, Sudbeck BD, Krane SM, Welgus HG, Parks WC: The activity of collagenase−1 is required for keratinocyte migration on a type I collagen matrix. J Cell Biol 1997, 137, 1445–1457.
  19. Senior RM, Griffin GL, Mecham R: Chemotactic activity of elastin−derived peptides. J Clin Invest 1980, 66, 859–862.
  20. Hunninghake GW, Davidson JM, Rennard S, Szapiel S, Gadek JE, Crystal G: Elastin fragments attract macrophage precursors to diseased sites in pulmonary emphysema. Science 1981, 212, 925–927.
  21. Gibbs DF, Warner RL, Weiss SJ, Johnson KJ, Varani J: Characterization of matrix metalloproteinases produced by rat alveolar macrophages. Am J Respir Cell Mol Biol 1999, 20, 1136–1144
  22. Barnes PJ: Chronic obstructive pulmonary disease. N Engl J Med 2000, 343, 269–280.
  23. Finlay GA, Russell KJ, McMahon KJ, Darcy EM, Masterson JB, FitzGerald MZ, O'Connor CM: Elevated levels of matrix metalloproteinases in bronchoalveolar lavage fluid of emphysematous patients. Thorax 1997, 52, 502–506.
  24. Collier IE, Wilhem SM, Eisen AZ et al.: H−ras oncogene−transformed human bronchial epithelial cells (TBE−1) secrete a single metalloproteinase capable of degrading membrane collagen. J Biol Chem 1988, 263, 6579–6587.
  25. Shipley JM, Doyle GAR, Fliszar CJ et al.: The structural basis for the elastolytic activity of the 92−kDa and 72−kDa gelatinases. J Biol Chem 1996, 271, 4335–4341.
  26. Segura−Valdez L, Pardo A, Gaxiola M, Uhal BD, Becerril C, Selman M: Upregulation of Gelatinases A and B, Collagenases 1 and 2, and Increased Parenchymal Cell Death in COPD. Chest 2000, 117, 684–694.
  27. Brajer B, Batura−Gabryel H, Nowicka A, Kuznar−Kaminska B, Szczepanik A: Concentration of matrix metalloproteinase−9 in serum of patients with chronic obstructive pulmonary disease and a degree of airway obstruction and disease progression. J Physiol Pharmacol 2008, 59, 145–152.
  28. Imai K, Dalal SS, Chen ES, Downey R, Schulman LL, Ginsburg M, and D'Armiento J: Human collagenase (matrix metalloproteinase−1) expression in the lungs of patients with emphysema. Am J Respir Crit Care Med 2001, 163, 786–791.
  29. Foronjy R, Nkyimbeng T, Wallace A et al.: Transgenic expression of matrix metalloproteinase−9 causes adultonset emphysema in mice associated with the loss of alveolar elastin. Am J Physiol Lung Cell Mol Physiol 2008, 294(6), L1149–L1157.
  30. Wallace AM, Sandford AJ, English JC et al.: Matrix metalloproteinase expression by human alveolar macrophages in relation to emphysema. COPD 2008, 5, 13–23.
  31. Lowrey GE, Henderson N, Blakey JD, Corne JM, Johnson SR: MMP−9 protein level does not reflect overall MMP activity in the airways of patients with COPD. Respir Med 2008, 102(6), 845–851.
  32. Lim S, Groneberg D, Fischer A, Oates T, Caramori G, Mattos W, Adcock I, Barnes PJ, Chung KF: Expression of heme oxygenase isoenzymes 1 and 2 in normal and asthmatic airways. Effect of inhaled corticosteroids. Am J Respir Crit Care Med 2000, 162, 1912–1918.
  33. Lim S, Roche N, Oliver BG, Mattos W, Barnes PJ, Fan CK: Balance of matrix metalloprotease−9 and tissue inhibitor of metalloprotease−1 from alveolar macrophages in cigarette smokers. Regulation by interleukin−10. Am J Respir Crit Care Med 2000, 162, 1355–1360.
  34. Russell RE, Thorley A, Culpitt SV, Dodd S, Donnelly LE, Demattos C, Fitzgerald M, Barnes PJ: Alveolar macrophage−mediated elastolysis: roles of matrix metalloproteinases, cysteine and serine proteases. Am J Physiol Lung Cell Mol Physiol 2002, 283, L867–L873.
  35. Cataldo D, Munaut C, Noel A, Frankenne F, Bartsch P, Foidart JM, Louis R: MMP−2− and MMP−9−linked gelatinolytic activity in the sputum from patients with asthma and chronic obstructive pulmonary disease. Int Arch Allergy Immunol 2000, 123, 259–267.
  36. Beeh KM, Beier J, Kornmann O, Buhl R: Sputum matrix metalloproteinase−9, tissue inhibitor of metalloprotinease−1 and their molar ratio in patients with chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis and healthy subjects. Respir Med 2003, 97, 634–639.
  37. Winkler MK, Foldes JK, Bunn RC, Fowlkes JL: Implications for matrix metalloproteinases as modulators of pediatric lung disease. Am J Physiol Lung Cell Mol Physiol 2003, 284, L557–L565.
  38. Owen CA, Hu Z, Barrick B, Shapiro SD: Inducible expression of tissue inhibitor of metalloproteinases−resistant matrix metalloproteinase−9 on the cell surface of neutrophils. Am J Respir Cell Mol Biol 2003, 29, 283–294.
  39. Owen CA, Hu Z, Lopez−Otin C, Shapiro SD: Membrane−bound matrix metalloproteinase−8 on activated polymorphonuclear cells is a potent, tissue inhibitor of metalloproteinase−resistant collagenase and serpinase. J Immunol 2004, 172, 7791–7803.
  40. Betsuyaku T, Tanino M, Nagai K, Nasuhara Y, Nishimura M, Senior RM: Extracellular matrix metalloproteinase inducer is increased in smokers' bronchoalveolar lavage fluid. Am J Respir Crit Care Med 2003, 168, 222–227.
  41. Bracke K, Cataldo D, Maes T, Gueders M, Noel A, Foidart JM, Brusselle G, Pauwels RA: Matrix metalloproteinase−12 and cathepsin D expression in pulmonary macrophages and dendritic cells of cigarette smokeexposed mice. Int Arch Allergy Immunol 2005, 138, 169–179.
  42. Hautamaki RD, Kobayashi DK, Senior RM et al.: Requirement for macrophage metalloelastase for cigarette smoke−induced emphysema in mice. Science 1997, 277, 2002–2004.
  43. Wang Z, Zheng T, Zhu Z, Homer RJ, Riese RJ, Chapman Jr HA, Shapiro SD, Elias JA: Interferon gamma induction of pulmonary emphysema in the adult murine lung. J Exp Med 2000, 192, 1587–1600.
  44. Dallas SL, Rosser JL, Mundy GR, Bonewald LF: Proteolysis of latent transforming growth factor−beta (TGF−beta)−binding protein−1 by osteoclasts. A cellular mechanism for release of TGF−beta from bone matrix. A cellular mechanism for release of TGF−beta from bone matrix. J Biol Chem 2002, 277, 21352–21360.
  45. Morris DG, Huang X, Kaminski N, Wang Y, Shapiro SD, Dolganov G, Glick A, Sheppard D: Loss of integrin alpha v beta6−mediated TGF−beta activation causes MMP12−dependent emphysema. Nature (London) 2003, 422, 169–173.
  46. Lanone S, Zheng T, Zhu Z, Liu W, Lee CG, Ma B, Chen Q, Homer RJ, Wang J, Rabach LA et al.: Overlapping and enzyme−specific contributions of matrix metalloproteinases−9 and −12 in IL−13−induced inflammation and remodeling. J Clin Invest 2002, 110, 463–474.
  47. Yu Q, Stamenkovic I: Cell surface−localized matrix metalloproteinase−9 proteolytically activates TGF−beta and promotes tumor invasion and angiogenesis. Genes Dev 2000, 14, 163–176.
  48. Minematsu N, Nakamura H, Tateno H, Nakajima T, Yamaguchi K: Genetic polymorphism in matrix metalloproteinase−9 and pulmonary emphysema. Biochem Biophys Res Commun 2001, 289, 116–119.
  49. Joos L, He JQ, Shepherdson MB, Connett JE, Anthonisen NR, Pare PD, Sandford AJ: The role of matrix metalloproteinase polymorphisms in the rate of decline in lung function. Hum Mol Genet 2002, 11, 569–576.
  50. Olson MW, Gervasi DC, Mobashery S et al.: Kinetic analysis of the binding of human matrix metalloproteinase−2 and −9 to tissue inhibitor of metalloproteinase (TIMP)−1 and TIMP−2. J Biol Chem 1997, 272, 29975–29983.
  51. Apte SS, Olsen BR, Murphy G: The gene structure of tissue inhibitor of metalloproteinases (TIMP)−3 and its inhibitory activities define the distinct TIMP gene family. J Biol Chem 1995, 270, 14313–14318.
  52. Baker EA, Stephenson TJ, Reed MW, Brown NJ: Expression of proteinases and inhibitors in human breast cancer progression and survival. Mol Pathol 2002, 55, 300–304.
  53. Pons AR, Sauleda J, Noguera A, Pons J, Barcelo B, Fuster A, Agusti AG: Decreased macrophage release of TGF−{beta} and TIMP−1 in chronic obstructive pulmonary disease. Eur Respir J 2005, 26, 60–66.
  54. Russell RE, Culpitt SV, DeMatos C, Donnelly L, Smith M, Wiggins J, Barnes PJ: Release and activity of matrix metalloproteinase−9 and tissue inhibitor of metalloproteinase−1 by alveolar macrophages from patients with chronic obstructive pulmonary disease. Am J Respir Cell Mol Biol 2002, 26, 602–609.
  55. Hirano K, Sakamoto T, Uchida Y, Morishima Y, Masuyama K, Ishii Y, Nomura A, Ohtsuka M, Sekizawa K: Tissue inhibitor of metalloproteinases−2 gene polymorphisms in chronic obstructive pulmonary disease. Eur Respir J 2001, 18, 748–752.
  56. Hegab AE, Sakamoto T, Uchida Y et al.: Association analysis of tissue inhibitor of metalloproteinase 2 gene polymorphisms with COPD in Egyptians. Respir Med 2005, 99(1), 107–110.
  57. Belvisi MG, Bottomley KM: The role of matrix metalloproteinases (MMPs) in the pathophysiology of chronic obstructive pulmonary disease (COPD): a therapeutic role for inhibitors of MMPs? Inflamm Res 2003, 52, 95–100.
  58. Selman M, Cisneros−Lira J, Gaxiola M, Ramirez R, Kudlacz EM, Mitchell PG, Pardo A: Matrix metalloproteinases inhibition attenuates tobacco smoke−induced emphysema in guinea pigs. Chest 2003, 123, 1633–1641.
  59. Hu J, Van Den Steen PE, Sang QX et al.: Matrix metalloproteinase inhibitors as therapy for inflammatory and vascular diseases. Nat Rev Drug Discov 2007, 6, 480–498.
  60. Churg A, Wang R, Wang X et al.: Effect of an MMP−9/MMP−12 inhibitor on smoke−induced emphysema and airway remodelling in guinea pigs. Thorax 2007, 62, 706–713.
  61. Mao JT, Tashkin DP, Belloni PN, Baileyhealy I, Baratelli F, Roth MD: All−trans retinoic acid modulates the balance of matrix metalloproteinase−9 and tissue inhibitor of metalloproteinase−1 in patients with emphysema. Chest 2003, 124, 1724–1732.
  62. Nagase H, Brew K: Designing TIMP (tissue inhibitor of metalloproteinases) variants that are selective metalloproteinase inhibitors. Biochem Soc Symp 2003, 70, 201–212.
© Wroclaw Medical University