Skip to main content
SpringerLink
Log in

The Extracellular Matrix of the Lung: The Forgotten Friend!

  • Conference paper
Intensive Care Medicine

  • 975 Accesses

Abstract

The extracellular matrix represents the three-dimensional scaffold of the alveolar wall, which is composed of a layer of epithelial and endothelial cells, their basement membrane, and a thin layer of interstitial space lying between the capillary endothelium and the alveolar epithelium [1]. In the segment where the epithelial and endothelial basement membranes are not fused, the interstitium is composed of cells, a macromolecular fibrous component, and the fluid phase of the extracellular matrix, functioning as a three dimensional mechanical scaffold characterized by a fibrous mesh consisting mainly of collagen types I and III, which provides tensile strength, and elastin conveying an elastic recoil [2, 3]. The three-dimensional fiber mesh is filled with other macromolecules, mainly glycosaminoglycans (GAGs), which are the major components of the non-fibrillar compartment of the interstitium [4]. In the lung, the extracellular matrix plays several roles, providing: a) mechanical tensile and compressive strength and elasticity; b) a low mechanical tissue compliance, thus contributing to the maintenance of normal interstitial fluid dynamics [5]; c) low resistive pathway for effective gas exchange [2]; d) control of cell behavior by binding of growth factors, chemokines, cytokines, and interaction with cell-surface receptors [6].

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. West JB, Mathieu-Costello O (1999) Structure, strength, failure, and remodeling of the pulmonary blood-gas barrier. Annu Rev Physiol 61:543–557

    Article  PubMed  CAS  Google Scholar 

  2. Suki B, Ito S, Stamenovic D, Lutchen KR, Ingenito EP (2005) Biomechanics of the lung parenchyma: critical roles of collagen and mechanical forces. J Appl Physiol 98:1892–1899

    Article  PubMed  Google Scholar 

  3. Rocco PR, Negri EM, Kurtz PM, et al (2001) Lung tissue mechanics and extracellular matrix remodeling in acute lung injury. Am J Respir Crit Care Med 164:1067–1071

    PubMed  CAS  Google Scholar 

  4. Negrini D, Passi A, De Luca G, Miserocchi G (2000) Matrix proteoglycans in development of pulmonary edema. In: Garg HG, Roughley PJ, Hales CA (eds) Proteoglycans in Lung Disease. Marcel Dekker, New York, pp 143–168

    Google Scholar 

  5. Miserocchi G, Negrini D, Del Fabbro M, Venturoli D (1993) Pulmonary interstitial pressure in intact in situ lung: The transition to interstitial edema. J Appl Physiol 74:1171–1177

    PubMed  CAS  Google Scholar 

  6. Johnson Z, Proudfoot A, Handel T (2005) Interaction of chemokines and glycosaminoglycans: A new twist in the regulation of chemokine function with opportunities for therapeutic interventions. Cytokine Growth Factors Rev 16:625–636

    Article  CAS  Google Scholar 

  7. Rocco PRM, Souza AB, Faffe DS, et al (2003) Effect of corticosteroid on lung parenchyma remodeling at an early phase of acute lung injury. Am J Respir Crit Care Med 168:677–684

    Article  PubMed  Google Scholar 

  8. Santos FB, Nagato LKS, Boechem NM, et al (2006) Time course of lung parenchyma remodelling in pulmonary and extrapulmonary acute lung injury. J Appl Physiol 100:98–106

    Article  PubMed  Google Scholar 

  9. Montes GS (1996) Structural biology of the fibres of the collagenous and elastic systems. Cell Biol Int 20:15–27

    Article  PubMed  CAS  Google Scholar 

  10. Mercer RR, Crapo JD (1990) Spatial distribution of collagen and elastin fibers in the lungs. J Appl Physiol 69:756–765

    PubMed  CAS  Google Scholar 

  11. Negri EM, Montes GS, Saldiva PHN, Cappelozzi VL (2000) Architectural remodelling in acute and chronic interstitial lung disease: fibrosis or fibroelastosis? Histopathology 37:393–401

    Article  PubMed  CAS  Google Scholar 

  12. Gerdin B, Hallgren R (1997) Dynamic role of hyaluronan (HYA) in connective tissue activation and inflammation. J Intern Med 242:49–55

    Article  PubMed  CAS  Google Scholar 

  13. Tammi MI, Day AJ, Turley EA (2002) Hyaluronan and homeostasis: a balancing act. J Biol Chem 277:4581–4584

    Article  PubMed  CAS  Google Scholar 

  14. Li Y, Rahmanian M, Widstrom C, Lepperdinger G, Frost GI, Heldin P (2000) Irradiation induced expression of hyaluronan (HA) synthase 2 and hyaluronidase 2 genes in rat lung tissue accompanies active turnover of HA and induction of types I and III collagen gene expression. Am J Respir Cell Mol Biol 23:411–418

    PubMed  CAS  Google Scholar 

  15. Cantor JO, Shteyngart B, Cerreta JM, Liu M, Armand G, Turino GM (2000) The effect of hyaluronan on elastic fiber injury in vitro and elastase-induced airspace enlargement in vivo. Proc Soc Exp Biol Med 225:65–71

    Article  PubMed  CAS  Google Scholar 

  16. Hardingham T, Fosang AJ (1992) Proteoglycans: many forms and many functions. FASEB J 6:861–870

    PubMed  CAS  Google Scholar 

  17. Nader H B, Dietrich C P, Buonassisi V, Colburn P (1987) Heparin sequences in the heparin sulfate chains of an endothelial cell proteoglycan. Proc Natl Acad Sci USA 84:3565–3569

    Article  PubMed  CAS  Google Scholar 

  18. Whitelock JM, Iozzo RV (2005) Heparan sulfate: a complex polymer charged with biological activity. Chem Rev 105:2745–2764

    Article  PubMed  CAS  Google Scholar 

  19. Poole A R (1986) Proteoglycans in health and disease: structures and functions. Biochem J 236:1–14

    PubMed  CAS  Google Scholar 

  20. Ruoss SJ, Gold WM, Caughey GH (1991) Mast cell exocytosis: evidence that granule proteoglycan processing is not coupled to degranulation. Biochem Biophys Res Commun 179:140–146

    Article  PubMed  CAS  Google Scholar 

  21. Roberts CR, Wight TN, Hascall VC (1997) Proteoglycans. In: Crystal RG, West JB, Weibel ER, Barnes PJ (eds) The Lung: Scientific Foundations. Lippincott-Raven, Philadelphia, pp 757–767

    Google Scholar 

  22. Iozzo RV, Murdoch AD (1996) Proteoglycans of the extracellular environment. Clues from the gene and protein side offer novel perspective in molecular diversity and function. FASEB J 10:598–614

    PubMed  CAS  Google Scholar 

  23. Yurchenko PD, Schittny JC (1990): Molecular architecture of basement membrane. FASEB J 4:1577–1590

    Google Scholar 

  24. Zhao J, Sime PJ, Bringas P Jr, Gauldie J, Warburton D (1999) Adenovirus — mediated decorin gene transfer prevents TGF-beta-induced inhibition of lung morphogenesis. Am J Physiol Lung Mol Cell Physiol 277:L412–422

    CAS  Google Scholar 

  25. Tumova S, Woods A, Couchman JR (2000) Heparan sulphate proteoglycans on the cell surface: versatile coordinators of cellular functions. Int J Biochem Cell Biol 32:269–288

    Article  PubMed  CAS  Google Scholar 

  26. Parks WC (2003) Matrix metalloproteinases in lung repair. Eur Respir J 44:S36–S38

    Article  CAS  Google Scholar 

  27. Lanchou J, Corbel M, Tanguy M (2003) 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 31:536–542

    Article  PubMed  CAS  Google Scholar 

  28. Miserocchi G, Negrini D, (1986) Contribution of Starling and Lymphatic flows to pleural liquid exchange in anesthetized rabbits. J Appl Physiol 61:325–330.

    PubMed  CAS  Google Scholar 

  29. Miserocchi G, Negrini D, Gonano C (1990) Direct measurements of interstitial pulmonary pressure in in situ lung with intact pleural space. J Appl Physiol 69:2168–2174

    PubMed  CAS  Google Scholar 

  30. Miserocchi G, Negrini D, Gonano C (1991) Parenchymal stress affects interstitial and pleural pressure in in situ lung. J Appl Physiol 71:1967–1972

    PubMed  CAS  Google Scholar 

  31. Miserocchi G, Nakamura T, Mariani E, Negrini D (1981) Pleural liquid pressure over the interlobar, mediastinal and diaphragmatic surfaces of the lung. Respir Physiol 46 61–69

    Article  PubMed  CAS  Google Scholar 

  32. Miserocchi G, Kelly S, Negrini D (1988) Pleural and extrapleural interstitial liquid pressure measured by cannulas and micropipettes. J Appl Physiol 65:555–562

    PubMed  CAS  Google Scholar 

  33. Negrini D, Cappelli C, Morini M, Miserocchi G (1987) Gravity dependent distribution of parietal subpleural interstitial pressure. J Appl Physiol 63:1912–1918

    PubMed  CAS  Google Scholar 

  34. Miserocchi G, Negrini D (1997) Pleural space: pressures and fluid dynamics. In: Crystal RG, West JB, Weibel ER, Barnes PJ (eds) The Lung: Scientific Foundations, 2nd edn. Lippincott-Raven, Philadelphia, pp 1217–1225

    Google Scholar 

  35. Negrini D, Passi A, De Luca G, Miserocchi G (1996) Pulmonary interstitial pressure and proteoglycans during development of pulmonary edema. Am J Physiol 270:H2000–H2007

    PubMed  CAS  Google Scholar 

  36. Passi A, Negrini D, Albertini R, De Luca G, Miserocchi G (1998) Involvement of lung interstitial proteoglycans in development of hydraulic and elastase induced edema. Am J Physiol 275:L631–L635

    PubMed  CAS  Google Scholar 

  37. Negrini D, Passi A, De Luca G, Miserocchi (1998) Proteoglycan involvement during development of lesional pulmonary edema. Am J Physiol 274:L203–L211

    PubMed  CAS  Google Scholar 

  38. Miserocchi G, Passi A, Negrini D, De Luca G, Del Fabbro M (2001) Pulmonary interstitial pressure and tissue matrix structure in acute hypoxia. Am J Physiol Lung Cell Mol Physiol L881–L887

    Google Scholar 

  39. Negrini D, Tenstad O, Passi A, Wiig H (2006) Differential degradation of matrix proteoglycans and edema development in rabbit lung. Am J Physiol Lung Cell Mol Physiol 290: L470–L477

    Article  PubMed  CAS  Google Scholar 

  40. D’Angelo E, Pecchiari M, Saetta M, Balestro E, Milich-Emili J (2004) Dependence of lung injury on inflation rate during low-volume ventilation in normal open-chest rabbits. J Appl Physiol 97:260–268

    Article  PubMed  Google Scholar 

  41. Duggan M, Mc Caul C, Mc Namara P, Engelberts D, Ackerey C, Kavanagh B (2003) Atelectasis causes vascular leak and lethal right ventricular failure in uninjured rat lungs. Am J Respir Crit Care Med 167:1633–1640

    Article  PubMed  Google Scholar 

  42. D’Angelo E, Pecchiari M, Baraggia M, Saetta M, Balestro E, Milic-Emili J (2002) Low-volume ventilation causes peripheral airway injury and increased airway resistance in normal rabbits. J Appl Physiol 92:949–956

    PubMed  Google Scholar 

  43. D’Angelo E, Pecchiari M, Delia Valle P, Koutsoukou A, Milich-Emili J (2005) Effects of mechanical ventilation at low lung volume on respiratory mechanics and nitric oxide exhalation in normal rabbits. J Appl Physiol 99:433–444

    Article  PubMed  CAS  Google Scholar 

  44. Negrini D, Moriondo A, Pelosi P, et al (2005) Metalloprotease activation in spontaneously breathing or mechanically ventilated anesthetized healthy rats. Experimental Biology. The FASEB Journal 19: A1605 (abst)

    Google Scholar 

  45. Al Jamal R, Ludwig MS (2001) Changes in proteoglycans and lung tissue mechanics during excessive mechanical ventilation in rats. Am J Physiol Lung Cell Mol Physiol 281:L1078–L1087

    Google Scholar 

  46. Farias LL, Faffe DS, Xisto DG, et al (2005) Positive end-expiratory pressure prevents lung mechanical stress caused by recruitment/derecruitment. J Appl Physiol 98:53–61

    Article  PubMed  Google Scholar 

  47. Chesnutt A, Matthay MA, Tibayan FA, Clark JG (1997) Detection of type III procollagen peptide in acute lung injury. Am J Respir Crit Care Med 156:840–845

    PubMed  CAS  Google Scholar 

  48. Duggan M, Kavanagh B (2005) Pulmonary atelectasis: A pathogenic perioperative entity. Anesthesiology 102:838–854

    Article  PubMed  Google Scholar 

  49. Tsuchida S, Engelberts D, Peltekova V, et al (2006) Atelectasis causes alveolar injury in nonatelectatic lung regions 174:279–289

    Google Scholar 

  50. Gattinoni L, Carlesso E, Carlingher P, Valenza F, Vagginelli F, Chiumello D (2003) Physical and biologycal triggers of ventilator induces lung injury and its prevention. Eur Respir J 22:15S–25S

    Article  Google Scholar 

  51. Moriondo A, Mukenge S, Negrini D (2006) Transmural pressure in rat initial subpleural lymphatics during spontaneous or mechanical ventilation. Am J Physiol Heart Circ Physiol 289:H263–H269

    Article  CAS  Google Scholar 

  52. Choi W, Quinn D, Park K, et al (2003) Systemic microvascular leak in an in vivo rat model of ventilator induced lung injury. Am J Respir Crit Care Med 167:1627–1632

    Article  PubMed  Google Scholar 

  53. Vlahakis N, Hubmayr R (2005) Cellular stress failure in ventilator-injured lungs. Am J Respir Crit Care Med 171:1328–1342

    Article  PubMed  Google Scholar 

  54. Belperio J, Keane M, Lynch J, Strieter M (2006) The role of cytokines during the pathogenesis of ventilator associated and ventilator induced lung injury. Semin Respir Crit Care Med 27:350–364

    Article  PubMed  Google Scholar 

  55. Tremblay L, Slutsky A (2006) Ventilator induced lung injury: From bench to bedside. Intensive Care Med 32:24–33

    Article  PubMed  Google Scholar 

  56. Halter J, Steinberg J, Schiller H, et al (2003) Positive end-expiratory pressure after a recruitment manoeuvre prevents both alveolar collapse and recruitment/derecruitment. Am J Respir Crit Care Med 2003;167:1620–1626

    Article  PubMed  Google Scholar 

  57. Berg JT, Fu Z, Breen EC, Tran HC, Mathieu-Costello O, West JB (1997) High lung inflation increases mRNA levels of extracellular matrix components and growth factors in lung parenchyma. J Appl Physiol 83:120–128

    PubMed  CAS  Google Scholar 

  58. Parker JC, Breen EC, West JB (1997) High vascular and airway pressures increase interstitial protein mRNA expression in isolated rat lungs. J Appl Physiol 83:1697–1705

    PubMed  CAS  Google Scholar 

  59. Garcia CS, Rocco PRM, Fachinetti LD, et al (2004) What increases type III procollagen mRNA levels in lung tissue: stress induced by changes in force or amplitude? Respir Physiol Neurobiol. 144:59–70

    Article  PubMed  CAS  Google Scholar 

  60. Quinn DA, Moufarrei RK, Volokhov A, Hales CA (2002) Interactions of lung stretch, hyoperoxia and MIP-2 production in ventilator induced lung injury. J Appl Physiol 93:517–525

    PubMed  CAS  Google Scholar 

  61. Uhlig S (2002) Ventilation-induced lung injury and mechanotransduction: stretching it too far? Am J Physiol Lung Cell Mol Physiol 2002; 282: L892–L896

    PubMed  CAS  Google Scholar 

  62. Garcia CS, Prota LF, Morales MM, Romero PV, Zin WA, Rocco PR (2006) Understanding the mechanisms of lung mechanics stress. Braz J Med Biol Res 39: 697–706

    PubMed  CAS  Google Scholar 

  63. Dreyfuss G, Ricard J, Saumon G (2003) On the physiology and clinical relevance of lungborne cytokines during ventilator induced lung injury. Am J Respir Crit Care Med 167:1467–1471

    Article  PubMed  Google Scholar 

  64. Belperio J, Keane M, Burdick M (2002) Critical role for cxcr2 and cxcr2 ligands during the pathogenesis of ventilator-induced lung injury. J Clin Invest 110:1703–1716

    Article  PubMed  CAS  Google Scholar 

  65. Vlahakis N, Hubmayr R (2005) Cellular stress failure in ventilator-injured lungs. Am J Respir Crit Care Med 171:1328–1342

    Article  PubMed  Google Scholar 

  66. Tremblay L, Valenza F, Ribeiro S, Li J, Slutsky A (1997) Injurious ventilatory strategies increase cytokines and c-fos m-rna expression in an isolated rat lung model. J Clin Invest 99:944–952

    Article  PubMed  CAS  Google Scholar 

  67. Ricard J, Dreyfuss D, Saumon G (2001) Production of inflammatory cytokines in ventilator induced lung injury: A reappraisal. Am J Respir Crit Care Med 163:1176–1180

    PubMed  CAS  Google Scholar 

  68. Bueno P, Bueno C, Santos M, et al (2002) Ventilation with high tidal volume induces inflammatory lung injury. Braz J Med Biol Res 35:191–198

    PubMed  CAS  Google Scholar 

  69. Haitsma J, Uhlig S, Goggel R, Verbrugge S, Lachmann U, Lachmann B (2000) Ventilator-induced lung injury leads to loss of alveolar and systemic ventilator-induced lung injury: Lessons from compartmentalization of tumor necrosis factor-alpha. Intensive Care Med 26:1515–1522

    Article  PubMed  CAS  Google Scholar 

  70. Tremblay L, Miatto D, Hamid O, Govindarajan A, Slutsky A (2002) Injurious ventilation induced widespread pulmonary epithelial expression of tumor necrosis factor-alpha and interleukin-6 messanger rna. Crit Care Med 30:1693–1700

    Article  PubMed  CAS  Google Scholar 

  71. Chiumello D, Pristine G, Slutsky A (1999) Mechanical ventilation affects local and systemic cytokines in an animal model of acute respiratory distress syndrome. Am J Respir Critical Care Med 160:109–116

    CAS  Google Scholar 

  72. Imai Y, Parodo J, Kagikawa J, et al (2003) Injurious mechanical ventilation and end-organ epithelial cell apoptosis and organ disfunction in an experimental model of acute respiratory distress syndrome. JAMA 289:2104–2112

    Article  PubMed  Google Scholar 

  73. Verbrugge S, Uhlig S, Neggers S, Martin C, Held H, Haitsma J, Lachmann B (1999) Different ventilation strategies affect lung function but do not increase TNF-alpha and PGI2 productions in lavaged rat lungs in vivo. Anesthesiology 91:1834–1843

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Anesthesiology B, Ospedale di Circolo e Fondazione Macchi, Viale Borri 57, 21100, Varese, Italy

    P. Pelosi

  2. Department of Ambient Health and Safety, University of Insubria, 21100, Varese, Italy

    P. Severgnini

  3. Department of Pulmonary Investigation, Carlos Chagas Filho Biophysics Institute, Federal University, Ilha do Fundao, 21949-900, Rio de Janeiro, Brazil

    P. R. Rocco

Authors
  1. P. Pelosi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. P. Severgnini
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. P. R. Rocco
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Intensive Care Erasme Hospital, Free University of Brussels, Route de Lennik 808, 1070, Brussels, Belgium

    Jean-Louis Vincent MD, PhD, FCCM, FCCP (Head) (Head)

Rights and permissions

Reprints and permissions

Copyright information

© 2007 Springer Science + Business Media Inc.

About this paper

Cite this paper

Pelosi, P., Severgnini, P., Rocco, P.R. (2007). The Extracellular Matrix of the Lung: The Forgotten Friend!. In: Vincent, JL. (eds) Intensive Care Medicine. Springer, New York, NY. https://doi.org/10.1007/978-0-387-49518-7_29

Download citation

  • DOI: https://doi.org/10.1007/978-0-387-49518-7_29

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-0-387-49517-0

  • Online ISBN: 978-0-387-49518-7

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation