Home LiteratureArticle Details
PMID: 16227332 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Review

Matrix metalloproteinases in destructive pulmonary pathology.

Thorax ·Vol. 61 ·No. 3 ·2006-03-00 ·Pages 259-66

Elkington PT, Friedland JS

Abstract

Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes that have a number of important physiological roles including remodelling of the extracellular matrix, facilitating cell migration, cleaving cytokines, and activating defensins. However, excess MMP activity may lead to tissue destruction. The biology of MMP and the role of these proteases in normal pulmonary immunity are reviewed, and evidence that implicates excess MMP activity in causing matrix breakdown in chronic obstructive pulmonary disease (COPD), acute respiratory distress syndrome (ARDS), sarcoidosis, and tuberculosis is discussed. Evidence from both clinical studies and animal models showing that stromal and inflammatory cell MMP expression leads to immunopathology is examined, and the mechanisms by which excess MMP activity may be targeted to improve clinical outcomes are discussed.

MeSH Terms
Animals Disease Models, Animal Humans Lung Diseases/etiology,therapy Matrix Metalloproteinases/physiology
Chemicals
Matrix Metalloproteinases
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Elkington P T G
Department of Infectious Diseases, Imperial College, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK. p.elkington@imperial.ac.uk
Friedland J S
References (115)
115 references, click to expand
  1. Inflammation dampened by gelatinase A cleavage of monocyte chemoattractant protein-3.
    Science. 2000 Aug 18;289(5482):1202-6 PMID: 10947989
  2. Collagenase and fibronectin in bronchoalveolar lavage fluid in patients with sarcoidosis.
    Thorax. 1988 May;43(5):393-400 PMID: 2848327
  3. The cysteine switch: a principle of regulation of metalloproteinase activity with potential applicability to the entire matrix metalloproteinase gene family.
    Proc Natl Acad Sci U S A. 1990 Jul;87(14):5578-82 PMID: 2164689
  4. Pulmonary disease progress in sarcoid patients with and without bronchoalveolar lavage collagenase.
    Am Rev Respir Dis. 1990 Sep;142(3):636-41 PMID: 2167622
  5. Neutral proteinases of human mononuclear phagocytes. Cellular differentiation markedly alters cell phenotype for serine proteinases, metalloproteinases, and tissue inhibitor of metalloproteinases.
    J Immunol. 1991 Feb 15;146(4):1286-93 PMID: 1991967
  6. Biochemistry and turnover of lung interstitium.
    Eur Respir J. 1990 Oct;3(9):1048-63 PMID: 2289553
  7. Matrix metalloproteinases and TIMP in acute respiratory distress syndrome.
    Am J Respir Crit Care Med. 1996 Aug;154(2 Pt 1):346-52 PMID: 8756805
  8. Extracellular matrix biology in the lung.
    Am J Physiol. 1996 Jan;270(1 Pt 1):L3-27 PMID: 8772523
  9. Increased expression of gelatinases and collagenase in rat lungs exposed to 100% oxygen.
    Am J Respir Crit Care Med. 1996 Oct;154(4 Pt 1):1067-75 PMID: 8887609
  10. Tobacco smoke-induced lung emphysema in guinea pigs is associated with increased interstitial collagenase.
    Am J Physiol. 1996 Nov;271(5 Pt 1):L734-43 PMID: 8944716
  11. Higher concentrations of matrix metalloproteinases in bronchoalveolar lavage fluid of patients with adult respiratory distress syndrome.
    Am J Respir Crit Care Med. 1997 Jan;155(1):43-6 PMID: 9001287
  12. Elevated levels of matrix metalloproteinases in bronchoalveolar lavage fluid of emphysematous patients.
    Thorax. 1997 Jun;52(6):502-6 PMID: 9227714
  13. Matrix metalloproteinase expression and production by alveolar macrophages in emphysema.
    Am J Respir Crit Care Med. 1997 Jul;156(1):240-7 PMID: 9230755
  14. Immunohistochemical study of matrix metalloproteinases and their tissue inhibitors in pulmonary Langerhans' cell granulomatosis.
    Arch Pathol Lab Med. 1997 Sep;121(9):930-7 PMID: 9302924
  15. Requirement for macrophage elastase for cigarette smoke-induced emphysema in mice.
    Science. 1997 Sep 26;277(5334):2002-4 PMID: 9302297
  16. Immunohistochemical study of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in pulmonary lymphangioleiomyomatosis (LAM).
    Hum Pathol. 1997 Sep;28(9):1071-8 PMID: 9308732
  17. Enhancement of fibroblast collagenase (matrix metalloproteinase-1) gene expression by ceramide is mediated by extracellular signal-regulated and stress-activated protein kinase pathways.
    J Biol Chem. 1998 Feb 27;273(9):5137-45 PMID: 9478967
  18. The immunopathogenesis of tuberculosis: a new working hypothesis.
    Trends Microbiol. 1998 Mar;6(3):94-7 PMID: 9582931
  19. Localization of matrix metalloproteinases-1, -2, and -9 and tissue inhibitor of metalloproteinase-2 in interstitial lung diseases.
    Lab Invest. 1998 Jun;78(6):687-98 PMID: 9645759
  20. Matrix metalloproteinase-mediated extracellular matrix protein degradation in human pulmonary emphysema.
    Lab Invest. 1998 Sep;78(9):1077-87 PMID: 9759652
  21. An immune basis for lung parenchymal destruction in chronic obstructive pulmonary disease and emphysema.
    PLoS Med. 2004 Oct;1(1):e8 PMID: 15526056
  22. Tissue inhibitor of metalloproteinase-1 deficiency amplifies acute lung injury in bleomycin-exposed mice.
    Am J Respir Cell Mol Biol. 2005 Sep;33(3):271-9 PMID: 15947421
  23. Mycobacterium tuberculosis up-regulates matrix metalloproteinase-1 secretion from human airway epithelial cells via a p38 MAPK switch.
    J Immunol. 2005 Oct 15;175(8):5333-40 PMID: 16210639
  24. Mycobacterium tuberculosis, but not vaccine BCG, specifically upregulates matrix metalloproteinase-1.
    Am J Respir Crit Care Med. 2005 Dec 15;172(12):1596-604 PMID: 16141443
  25. Changes in collagen turnover in early acute respiratory distress syndrome.
    Am J Respir Crit Care Med. 1999 Dec;160(6):1910-5 PMID: 10588605
  26. Tissue inhibitors of metalloproteinases: evolution, structure and function.
    Biochim Biophys Acta. 2000 Mar 7;1477(1-2):267-83 PMID: 10708863
  27. TIMP-1, -2, -3, and -4 in idiopathic pulmonary fibrosis. A prevailing nondegradative lung microenvironment?
    Am J Physiol Lung Cell Mol Physiol. 2000 Sep;279(3):L562-74 PMID: 10956632
  28. Treatment with BB-94, a broad spectrum inhibitor of zinc-dependent metalloproteinases, causes deviation of the cytokine profile towards type-2 in experimental pulmonary tuberculosis in Balb/c mice.
    Int J Exp Pathol. 2000 Jun;81(3):199-209 PMID: 10971741
  29. Induction of MMP-9 mediated gelatinolytic activity in human monocytic cells by cell wall components of Mycobacterium tuberculosis.
    Microb Pathog. 2000 Oct;29(4):231-44 PMID: 10993742
  30. The serpin alpha1-proteinase inhibitor is a critical substrate for gelatinase B/MMP-9 in vivo.
    Cell. 2000 Sep 1;102(5):647-55 PMID: 11007483
  31. Neutrophil gelatinase B potentiates interleukin-8 tenfold by aminoterminal processing, whereas it degrades CTAP-III, PF-4, and GRO-alpha and leaves RANTES and MCP-2 intact.
    Blood. 2000 Oct 15;96(8):2673-81 PMID: 11023497
  32. 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 Oct;162(4 Pt 1):1355-60 PMID: 11029344
  33. Inducible targeting of IL-13 to the adult lung causes matrix metalloproteinase- and cathepsin-dependent emphysema.
    J Clin Invest. 2000 Nov;106(9):1081-93 PMID: 11067861
  34. Characteristic elevation of matrix metalloproteinase activity in idiopathic interstitial pneumonias.
    Am J Respir Crit Care Med. 2000 Nov;162(5):1949-56 PMID: 11069839
  35. Interferon gamma induction of pulmonary emphysema in the adult murine lung.
    J Exp Med. 2000 Dec 4;192(11):1587-600 PMID: 11104801
  36. Ionizing radiation enhances matrix metalloproteinase-2 production in human lung epithelial cells.
    Am J Physiol Lung Cell Mol Physiol. 2001 Jan;280(1):L30-8 PMID: 11133492
  37. Identification of a matrix-degrading phenotype in human tuberculosis in vitro and in vivo.
    J Immunol. 2001 Mar 15;166(6):4223-30 PMID: 11238675
  38. Human collagenase (matrix metalloproteinase-1) expression in the lungs of patients with emphysema.
    Am J Respir Crit Care Med. 2001 Mar;163(3 Pt 1):786-91 PMID: 11254539
  39. Identification and enzymatic characterization of two diverging murine counterparts of human interstitial collagenase (MMP-1) expressed at sites of embryo implantation.
    J Biol Chem. 2001 Mar 30;276(13):10253-62 PMID: 11113146
  40. The role of metalloelastase in immune complex-induced acute lung injury.
    Am J Pathol. 2001 Jun;158(6):2139-44 PMID: 11395391
  41. Occurrence of matrix metalloproteinases and tissue inhibitors of metalloproteinases in tuberculous pleuritis.
    Tuberculosis (Edinb). 2001;81(3):203-9 PMID: 11466032
  42. Transendothelial migration of lymphocytes across high endothelial venules into lymph nodes is affected by metalloproteinases.
    Blood. 2001 Aug 1;98(3):688-95 PMID: 11468168
  43. Metalloproteinase inhibition prevents acute respiratory distress syndrome.
    J Surg Res. 2001 Aug;99(2):245-52 PMID: 11469893
  44. Production of matrix metalloproteinases in response to mycobacterial infection.
    Infect Immun. 2001 Sep;69(9):5661-70 PMID: 11500442
  45. Spontaneous air space enlargement in the lungs of mice lacking tissue inhibitor of metalloproteinases-3 (TIMP-3).
    J Clin Invest. 2001 Sep;108(6):817-29 PMID: 11560951
  46. Gelatinase B: a tuner and amplifier of immune functions.
    Trends Immunol. 2001 Oct;22(10):571-9 PMID: 11574282
  47. Alveolar macrophage deficiency in osteopetrotic mice deficient in macrophage colony-stimulating factor is spontaneously corrected with age and associated with matrix metalloproteinase expression and emphysema.
    Blood. 2001 Nov 1;98(9):2845-52 PMID: 11675359
  48. Regulation of matrilysin expression in airway epithelial cells by Pseudomonas aeruginosa flagellin.
    J Biol Chem. 2001 Nov 2;276(44):41417-23 PMID: 11527977
  49. Matrix metalloproteinases in lung biology.
    Respir Res. 2001;2(1):10-9 PMID: 11686860
  50. Role of stromelysin 1 and gelatinase B in experimental acute lung injury.
    Am J Respir Cell Mol Biol. 2001 May;24(5):537-44 PMID: 11350822
  51. M. tuberculosis induction of matrix metalloproteinase-9: the role of mannose and receptor-mediated mechanisms.
    Am J Physiol Lung Cell Mol Physiol. 2002 Mar;282(3):L546-55 PMID: 11839551
  52. 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 May;26(5):602-9 PMID: 11970913
  53. Matrix metalloproteinases: a tail of a frog that became a prince.
    Nat Rev Mol Cell Biol. 2002 Mar;3(3):207-14 PMID: 11994741
  54. The role of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in cryptogenic organizing pneumonia.
    Chest. 2002 May;121(5):1478-85 PMID: 12006432
  55. Circulation level of matrix metalloproteinase-9 is correlated with disease severity in tuberculosis patients.
    Int J Tuberc Lung Dis. 2002 Aug;6(8):713-9 PMID: 12150484
  56. Overlapping and enzyme-specific contributions of matrix metalloproteinases-9 and -12 in IL-13-induced inflammation and remodeling.
    J Clin Invest. 2002 Aug;110(4):463-74 PMID: 12189240
  57. Alveolar macrophage-mediated elastolysis: roles of matrix metalloproteinases, cysteine, and serine proteases.
    Am J Physiol Lung Cell Mol Physiol. 2002 Oct;283(4):L867-73 PMID: 12225964
  58. Induced sputum-retrieved matrix metalloproteinase 9 and tissue metalloproteinase inhibitor 1 in granulomatous diseases.
    Clin Exp Immunol. 2002 Nov;130(2):331-7 PMID: 12390324
  59. Matrix metalloproteases in BAL fluid of patients with cystic fibrosis and their modulation by treatment with dornase alpha.
    Thorax. 2002 Nov;57(11):930-4 PMID: 12403873
  60. Matrix metalloproteinases and tissue inhibitor of metalloproteinase-1 in sarcoidosis and IPF.
    Eur Respir J. 2002 Nov;20(5):1220-7 PMID: 12449177
  61. Matrilysin shedding of syndecan-1 regulates chemokine mobilization and transepithelial efflux of neutrophils in acute lung injury.
    Cell. 2002 Nov 27;111(5):635-46 PMID: 12464176
  62. Alpha1-antitrypsin polymerization and the serpinopathies: pathobiology and prospects for therapy.
    J Clin Invest. 2002 Dec;110(11):1585-90 PMID: 12464660
  63. Role of matrix metalloproteinases in asthma.
    Curr Opin Pulm Med. 2003 Jan;9(1):28-33 PMID: 12476081
  64. Matrix metalloproteinase-9 in lung remodeling.
    Am J Respir Cell Mol Biol. 2003 Jan;28(1):12-24 PMID: 12495928
  65. Matrix metalloproteinases and their tissue inhibitors in the lesions of cardiac and pulmonary sarcoidosis: an immunohistochemical study.
    Hum Pathol. 2002 Dec;33(12):1158-64 PMID: 12514782
  66. Imbalance between matrix metalloproteinases (MMP-9 and MMP-2) and tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) in acute respiratory distress syndrome patients.
    Crit Care Med. 2003 Feb;31(2):536-42 PMID: 12576963
  67. Pulmonary matrix metalloproteinase excess in hospital-acquired pneumonia.
    Am J Respir Crit Care Med. 2003 Feb 15;167(4):593-8 PMID: 12588713
  68. Loss of integrin alpha(v)beta6-mediated TGF-beta activation causes Mmp12-dependent emphysema.
    Nature. 2003 Mar 13;422(6928):169-73 PMID: 12634787
  69. Tissue inhibitor of metalloproteinase-3 downregulation in lymphangioleiomyomatosis: potential consequence of abnormal serum response factor expression.
    Am J Respir Cell Mol Biol. 2003 Apr;28(4):504-11 PMID: 12654640
  70. Progressive adult-onset emphysema in transgenic mice expressing human MMP-1 in the lung.
    Am J Physiol Lung Cell Mol Physiol. 2003 May;284(5):L727-37 PMID: 12676763
  71. Generation of biologically active IL-1 beta by matrix metalloproteinases: a novel caspase-1-independent pathway of IL-1 beta processing.
    J Immunol. 1998 Oct 1;161(7):3340-6 PMID: 9759850
  72. Matrilysin expression and function in airway epithelium.
    J Clin Invest. 1998 Oct 1;102(7):1321-31 PMID: 9769324
  73. The alveolar space is the site of intense inflammatory and profibrotic reactions in the early phase of acute respiratory distress syndrome.
    Crit Care Med. 1999 Feb;27(2):304-12 PMID: 10075054
  74. Regulatory effects of endogenous protease inhibitors in acute lung inflammatory injury.
    J Immunol. 1999 Mar 15;162(6):3653-62 PMID: 10092827
  75. Overexpression of alveolar macrophage gelatinase B (MMP-9) in patients with idiopathic pulmonary fibrosis: effects of steroid and immunosuppressive treatment.
    Am J Respir Cell Mol Biol. 1999 May;20(5):903-13 PMID: 10226060
  76. Neutrophil granule proteins in bronchoalveolar lavage fluid from subjects with subclinical emphysema.
    Am J Respir Crit Care Med. 1999 Jun;159(6):1985-91 PMID: 10351949
  77. Matrix metalloproteinase inhibitor prevents acute lung injury after cardiopulmonary bypass.
    Circulation. 1999 Jul 27;100(4):400-6 PMID: 10421601
  78. Airway epithelial cell migration dynamics. MMP-9 role in cell-extracellular matrix remodeling.
    J Cell Biol. 1999 Jul 26;146(2):517-29 PMID: 10427102
  79. Regulation of intestinal alpha-defensin activation by the metalloproteinase matrilysin in innate host defense.
    Science. 1999 Oct 1;286(5437):113-7 PMID: 10506557
  80. Matrix metalloproteinases 2, 9, and 13, and tissue inhibitors of metalloproteinases 1 and 2 in experimental lung silicosis.
    Am J Respir Crit Care Med. 1999 Oct;160(4):1274-82 PMID: 10508819
  81. Collagenolytic activity in amphibian tissues: a tissue culture assay.
    Proc Natl Acad Sci U S A. 1962 Jun 15;48:1014-22 PMID: 13902219
  82. A matrix metalloproteinase inhibitor promotes granuloma formation during the early phase of Mycobacterium tuberculosis pulmonary infection.
    Tuberculosis (Edinb). 2004;84(6):387-96 PMID: 15525562
  83. Mediators of chronic obstructive pulmonary disease.
    Pharmacol Rev. 2004 Dec;56(4):515-48 PMID: 15602009
  84. Induced sputum matrix metalloproteinase-9 correlates with lung function and airway inflammation in children with cystic fibrosis.
    Pediatr Pulmonol. 2005 Mar;39(3):224-32 PMID: 15635615
  85. Proteases and emphysema.
    Curr Opin Pulm Med. 2005 Mar;11(2):153-9 PMID: 15699789
  86. PAR1 is a matrix metalloprotease-1 receptor that promotes invasion and tumorigenesis of breast cancer cells.
    Cell. 2005 Feb 11;120(3):303-13 PMID: 15707890
  87. Matrix metalloproteinase-9 in bronchiolitis obliterans syndrome after lung transplantation.
    Eur Respir J. 2005 Mar;25(3):494-501 PMID: 15738294
  88. Expression of matrix metalloproteinase-9 in pleural effusions of tuberculosis and lung cancer.
    Respiration. 2005 Mar-Apr;72(2):166-75 PMID: 15824527
  89. Broncho-alveolar lavage matrix metalloproteases as a sensitive measure of bronchiolitis obliterans.
    Am J Transplant. 2005 Jun;5(6):1548-52 PMID: 15888067
  90. Matrix metalloproteinase inhibitors and cancer: trials and tribulations.
    Science. 2002 Mar 29;295(5564):2387-92 PMID: 11923519
  91. Matrix metalloproteinases inhibition attenuates tobacco smoke-induced emphysema in Guinea pigs.
    Chest. 2003 May;123(5):1633-41 PMID: 12740284
  92. Differential regulation of lipopolysaccharide-induced monocyte matrix metalloproteinase (MMP)-1 and MMP-9 by p38 and extracellular signal-regulated kinase 1/2 mitogen-activated protein kinases.
    J Immunol. 2003 Jun 15;170(12):6244-9 PMID: 12794156
  93. Matrix metalloproteinase-9-mediated dendritic cell recruitment into the airways is a critical step in a mouse model of asthma.
    J Immunol. 2003 Jul 15;171(2):1016-22 PMID: 12847275
  94. Metalloproteinase inhibition reduces lung injury and improves survival after cecal ligation and puncture in rats.
    J Surg Res. 2003 May 15;111(2):185-95 PMID: 12850461
  95. Matrilysin-dependent elastolysis by human macrophages.
    J Exp Med. 2003 Sep 15;198(6):925-35 PMID: 12963695
  96. Negative impact of tissue inhibitor of metalloproteinase-3 null mutation on lung structure and function in response to sepsis.
    Am J Physiol Lung Cell Mol Physiol. 2003 Dec;285(6):L1222-32 PMID: 12909586
  97. Unopposed matrix metalloproteinase-9 expression in human tuberculous granuloma and the role of TNF-alpha-dependent monocyte networks.
    J Immunol. 2003 Nov 15;171(10):5579-86 PMID: 14607966
  98. Mycobacterium tuberculosis growth at the cavity surface: a microenvironment with failed immunity.
    Infect Immun. 2003 Dec;71(12):7099-108 PMID: 14638800
  99. Lymphoid tissue and emphysema in the lungs of transgenic mice inducibly expressing tumor necrosis factor-alpha.
    Am J Respir Cell Mol Biol. 2004 Apr;30(4):438-48 PMID: 12972399
  100. Immunity to tuberculosis.
    Annu Rev Immunol. 2004;22:599-623 PMID: 15032590
  101. Extracellular regulated kinase/mitogen activated protein kinase is up-regulated in pulmonary emphysema and mediates matrix metalloproteinase-1 induction by cigarette smoke.
    J Biol Chem. 2004 Apr 23;279(17):17690-6 PMID: 14764579
  102. Matrix metalloproteinases as modulators of inflammation and innate immunity.
    Nat Rev Immunol. 2004 Aug;4(8):617-29 PMID: 15286728
  103. Tumor necrosis factor-alpha drives 70% of cigarette smoke-induced emphysema in the mouse.
    Am J Respir Crit Care Med. 2004 Sep 1;170(5):492-8 PMID: 15184206
  104. Macrophage activation by mycobacterial water soluble compounds and synthetic muramyl dipeptide.
    J Immunol. 1979 Jun;122(6):2226-31 PMID: 221582
  105. Marked longevity of human lung parenchymal elastic fibers deduced from prevalence of D-aspartate and nuclear weapons-related radiocarbon.
    J Clin Invest. 1991 May;87(5):1828-34 PMID: 2022748
  106. Elastin degradation by mononuclear phagocytes.
    Ann N Y Acad Sci. 1991;624:69-80 PMID: 2064250
  107. Collagenase expression in the lungs of transgenic mice causes pulmonary emphysema.
    Cell. 1992 Dec 11;71(6):955-61 PMID: 1458541
  108. Processing of tumour necrosis factor-alpha precursor by metalloproteinases.
    Nature. 1994 Aug 18;370(6490):555-7 PMID: 8052310
  109. Effect of Mycobacterium tuberculosis and its components on macrophages and the release of matrix metalloproteinases.
    Thorax. 1996 Mar;51(3):306-11 PMID: 8779137
  110. Degradation of interleukin 1beta by matrix metalloproteinases.
    J Biol Chem. 1996 Jun 21;271(25):14657-60 PMID: 8663297
  111. Expression of matrix metalloproteinase gelatinases A and B by cultured epithelial cells from human bronchial explants.
    J Biol Chem. 1996 Jun 28;271(26):15580-9 PMID: 8663061
  112. Upregulation of gelatinases A and B, collagenases 1 and 2, and increased parenchymal cell death in COPD.
    Chest. 2000 Mar;117(3):684-94 PMID: 10712992
  113. The acute respiratory distress syndrome.
    N Engl J Med. 2000 May 4;342(18):1334-49 PMID: 10793167
  114. Increased metalloproteinase activity, oxidant production, and emphysema in surfactant protein D gene-inactivated mice.
    Proc Natl Acad Sci U S A. 2000 May 23;97(11):5972-7 PMID: 10801980
  115. Gelatinase B is required for alveolar bronchiolization after intratracheal bleomycin.
    Am J Pathol. 2000 Aug;157(2):525-35 PMID: 10934155
Article Info
Journal
Thorax
Abbr.
Thorax
ISSN
0040-6376
DOI
10.1136/thx.2005.051979
Email
p.elkington@imperial.ac.uk
Published
2006-03-00
Epub
2005-00-14
Pages
259-66
Language
English
Region
England
NLM ID
0417353
PMCID
PMC2080735
Subset
IM
Grants
Wellcome Trust · United Kingdom
External Links
PubMed source DOI: 10.1136/thx.2005.051979 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2