Lung Parenchyma Remodelling in the Acute Respiratory Distress Syndrome

  • A. B. Souza-Fernandes
  • P. R. M. Rocco
  • W. A. Zin


The acute respiratory distress syndrome (ARDS) is a catastrophic condition with exudation, inflammation and often fibrosis throughout the lung [1]. Interestingly, despite the extensive damage, it can be fully repaired [2]. This recovery requires the resolution of inflammation, clearance of inflammatory cells and oedema and reversal of fibrosis, allowing the lung tissue to return to its normal structure and function. The repair process is very complex and modulated not only by several growth factors and cytokines released in the alveolar space during lung injury, but also by a variety of components of the extracellular matrix (ECM) [3].


Acute Lung Injury Idiopathic Pulmonary Fibrosis Acute Respiratory Distress Syndrome Elastic Fibre Respir Crit 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Luce JM (1998) Acute lung injury and the acute respiratory distress syndrome. Crit Care Med 26:369–378PubMedCrossRefGoogle Scholar
  2. 2.
    McHugh LG, Milberg JA, Whitcomb ME et al (1994) Recovery of function in survivors of the acute respiratory distress syndrome. Am J Respir Crit Care Med 150:90–94PubMedGoogle Scholar
  3. 3.
    Geiser T (2003) Mechanisms of alveolar epithelial repair in acute lung injury — a translational approach. Swiss Med Wkly 133:586–590PubMedGoogle Scholar
  4. 4.
    Bernard GR, Artigas A, Bringham KL et al (1994) The American-European consensus conference on ARDS: definitions, mechanisms, relevant outcome, and clinical trial coordination. Am J Respir Crit Care Med 149:818–824PubMedGoogle Scholar
  5. 5.
    Wiener-Kronish JP, Albertine KH, Matthay MA (1991) Differential response of the endothelial and epithelial barrier of the lung in sheep to Escherichia coli endotoxin. J Clin Invest 88:864–875PubMedGoogle Scholar
  6. 6.
    Pelosi P, D’Onofrio D, Chiumello D (2003) Pulmonary and extrapulmonary acute respiratory distress syndrome are different. Eur Respir J 22:S48–S56CrossRefGoogle Scholar
  7. 7.
    Rocco PRM, Zin WA (2005) Pulmonary and extrapulmonary acute respiratory distress syndrome: are they diffent? Curr Opin Crit Care 11:10–17PubMedCrossRefGoogle Scholar
  8. 8.
    Menezes SL, Bozza PT, Neto HC et al (2005) Pulmonary and extrapulmonary acute lung injury: inflammatory and ultrastructural analyses. J Appl Physiol 98:1777–1783PubMedCrossRefGoogle Scholar
  9. 9.
    Ware LB (2005) Prognostic determinants of acute respiratory distress syndrome in adults: impact on clinical trial design. Crit Care Med 33:S217–S222PubMedCrossRefGoogle Scholar
  10. 10.
    Vincent J-L, Sakr Y, Raniere VM (2003) Epidemiology and outcome of acute respiratory failure in intensive care unit patients. Crit Care Med 31:S296–S299PubMedCrossRefGoogle Scholar
  11. 11.
    Piantadosi CA, Schwartz DA (2004) The acute respiratory distress syndrome. Ann Intern Med 141:460–470PubMedGoogle Scholar
  12. 12.
    Ware LB, Matthay MA (2000) The acute respiratory distress syndrome. N Engl J Med 342:1334–1349PubMedCrossRefGoogle Scholar
  13. 13.
    Davidson TA, Caldwell ES, Curtis JR et al (1999) Reduced quality of life in survivors of acute respiratory distress syndrome compared with critically ill control patients. JAMA 281:354–360PubMedCrossRefGoogle Scholar
  14. 14.
    Herridge MS, Cheung AM, Tansey CM et al (2003) One-year outcome in survivors of acute respiratory distress syndrome. N Engl J Med 384:683–693CrossRefGoogle Scholar
  15. 15.
    Mendez JL, Hubmayr RD (2005) New insights into the pathology of acute respiratory failure. Curr Opin Crit Care 11:29–36PubMedCrossRefGoogle Scholar
  16. 16.
    Fukuda Y, Ishizaki M, Masuda Y et al (1987) The role of intraalveolar fibrosis in the process of pulmonary structural remodeling in patients with diffuse alveolar damage. Am J Pathol 126:171–182PubMedGoogle Scholar
  17. 17.
    Takahashi T, Takahashi Y, Nio M (1994) Remodeling of the alveolar structure in the paraquat lung of humans: a morphometric study. Hum Pathol 25:702–708PubMedCrossRefGoogle Scholar
  18. 18.
    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 164:1067–1071PubMedGoogle Scholar
  19. 19.
    Rocco PR, 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 168:677–684PubMedCrossRefGoogle Scholar
  20. 20.
    Stanley MV, Henry-Stanly MJ, Gajl-Peczalska KJ et al (1992) Hyperplasia of type II penumocytes in acute lung injury: cytologic findings of sequential bronchoalveolar lavage. Am J Clin Pathol 97:669–667PubMedGoogle Scholar
  21. 21.
    Haitsma JJ, Papadakos PJ, Lachmann B (2004) Surfactant therapy for acute lung injury/acute respiratory distress syndrome. Curr Opin Crit Care 10:18–22PubMedCrossRefGoogle Scholar
  22. 22.
    Homma S, Jones R, Qvist J et al (1992) Pulmonary vascular lesions in the adult respiratory distress syndrome caused by inhalation of zinc chloride smoke: a morphometric study. Hum Pathol 23:45–50PubMedCrossRefGoogle Scholar
  23. 23.
    Pelosi P (2000) What about primary and secondary ARDS. Minerva Anestesiol 66:779–785PubMedGoogle Scholar
  24. 24.
    Armstrong L, Thickett DR, Mansell JP et al (1999) Changes in collagen turnover in early acute respiratory distress syndrome. Am J Respir Crit Care Med 160:1910–1915PubMedGoogle Scholar
  25. 25.
    Raghow R (1994) The role of extracellular matrix in postinflammatory wound healing and fibrosis. FASEB J 8:823–831PubMedGoogle Scholar
  26. 26.
    Montes GS (1996) Structural biology of the fibres of the collagenous and elastic systems. Cell Biol Int 20:15–27PubMedCrossRefGoogle Scholar
  27. 27.
    Starcher BC (2000) Lung elastin and matrix. Chest 117:S229–S234CrossRefGoogle Scholar
  28. 28.
    Chesnutt AN, Matthay MA, Tibayan FA et al (1997) Early detection of type III procollagen peptide in acute lung injury. Pathogenetic and prognostic significance. Am J Respir Crit Care Med 156:840–845PubMedGoogle Scholar
  29. 29.
    Liebler JM, Qu Z, Buckner B et al (1998) Fibroproliferation and mast cells in the acute respiratory distress syndrome. Thorax 53:823–829PubMedCrossRefGoogle Scholar
  30. 30.
    Meduri GU, Tolley EA, Chinn A et al (1998) Procollagen types I and III aminoterminal propeptide levels during acute respiratory distress syndrome and in response to methylprednisolone treatment. Am J Respir Crit Care Med 158:1432–1441PubMedGoogle Scholar
  31. 31.
    Pugin J, Verghese G, Widmer MC et al (1999) The alveolar space is the site of intense inflammatory and profibrotic reactions in the early phase of acute respiratory distress syndrome. Crit Care Med 27:304–312PubMedCrossRefGoogle Scholar
  32. 32.
    Ebihara T, Venkatesan N, Tanaka R et al (2000) Changes in extracellular matrix and tissue viscoelasticity in bleomycin-induced lung fibrosis. Temporal aspects. Am J Respir Crit Care Med 162:1569–1576PubMedGoogle Scholar
  33. 33.
    Geiser T (2003) Idiopathic pulmonary fibrosis — a disorder of alveolar wound repair? Swiss Med Wkly 133:405–411PubMedGoogle Scholar
  34. 34.
    Corbel M, Boichot E, Lagente V (2000) Role of gelatinases MMP-2 and MMP-9 in tissue remodeling following acute lung injury. Braz J Med Biol Res 33:749–754PubMedCrossRefGoogle Scholar
  35. 35.
    Parks WC (2003) Matrix metalloproteinases in lung repair. Eur Respir J 44:S36–S38CrossRefGoogle Scholar
  36. 36.
    Pardo A, Selman M (1996) Matrix metalloproteinases and lung injury. Braz J Med Biol Res 2:1109–1115Google Scholar
  37. 37.
    Ingbar DH (2000) Mechanisms of repair and remodeling following acute lung injury. Clin Chest Med 21:589–616PubMedCrossRefGoogle Scholar
  38. 38.
    Bellingan GJ (2002) Resolution of inflammation and repair. European Respiratory Monograph 7:70–82Google Scholar
  39. 39.
    Chapman HA (2004) Disorders of lung matrix remodeling. J Clin Invest 113:148–157PubMedCrossRefGoogle Scholar
  40. 40.
    Marshall BC, Brown BR, Rothstein MA et al (1991) Alveolar epithelial cells express both plasminogen activator and tissue factor. Potential role in repair of lung injury. Chest 99:S25–S27Google Scholar
  41. 41.
    Panos RJ, Rubin JS, Csaky KG et al (1993) Keratinocyte growth factor and hepatocyte growth factor/scatter factor are heparin-binding growth factors for alveolar type II cells in fibroblast-conditioned medium. J Clin Invest 92:969–977PubMedCrossRefGoogle Scholar
  42. 42.
    Orfanos SE, Mavrommati I, Korovesi I et al (2004) Pulmonary endothelium in acute lung injury: from basic science to the critically ill. Intensive Care Med 9:1702–1714Google Scholar
  43. 43.
    Dudek SM, Garcia JG (2001) Cytoskeletal regulation of pulmonary vascular permeability. J Appl Physiol 91:1487–1500PubMedGoogle Scholar
  44. 44.
    Kaner RJ, Ladetto JV, Singh R et al (2000) Lung overexpression of the vascular endothelial growth factor gene induces pulmonary edema. Am J Respir Cell Mol Biol 22:657–664PubMedGoogle Scholar
  45. 45.
    Compernolle V, Brusselmans K, Acker T et al (2002) Loss of HIF-2alpha and inhibition of VEGF impair fetal lung maturation, whereas treatment with VEGF prevents fatal respiratory distress in premature mice. Nat Med 8:702–710PubMedGoogle Scholar
  46. 46.
    Brown SB, Savill J (1999) Phagocytosis triggers macrophage release of Fas ligand and induces apoptosis of bystander leukocytes. J Immunol 162:480–485PubMedGoogle Scholar
  47. 47.
    Gerber HP, McMurtrey A, Kowalski J et al (1998) Vascular endothelial growth factor regulates endothelial cell survival through the phosphatidylinositol 3′-kinase/Akt signal transduction pathway. Requirement for Flk-1/KDR activation. J Biol Chem 273:30336–30343PubMedCrossRefGoogle Scholar
  48. 48.
    Mura M, dos Santos CC, Stewart D et al (2004) Vascular endothelial growth factor and related molecules in acute lung injury. J Appl Physiol 97:1605–1617PubMedCrossRefGoogle Scholar
  49. 49.
    Block ER (1992) Pulmonary endothelial cell pathobiology: implications for acute lung injury. Am J Med Sci 304:136–144PubMedCrossRefGoogle Scholar
  50. 50.
    Liu SF, Crawley DE, Barnes PJ et al (1991) Endothelium-derived relaxing factor inhibits hypoxic pulmonary vasoconstriction in rats. Am Rev Respir Dis 143:32–37PubMedGoogle Scholar
  51. 51.
    Martin TR, Nakamura M, Matute-Bello G (2003) The role of apoptosis in acute lung injury. Crit Care Med 31:S184–S188PubMedCrossRefGoogle Scholar
  52. 52.
    Uhal BD (2002) Apoptosis in lung fibrosis and repair. Chest 122:293S–298SPubMedCrossRefGoogle Scholar
  53. 53.
    Li HP, Li X, He GJ et al (2004) The influence of dexamethasone on the proliferative and apoptosis of pulmonary inflammatory cells in bleomycin-induced fibrosis in rats. Respirology 9:25–32PubMedCrossRefGoogle Scholar
  54. 54.
    Li X, Shu R, Filippatos G et al (2004) Apoptosis in lung injury and remodeling. J Appl Physiol 91:1535–1542CrossRefGoogle Scholar
  55. 55.
    Bardales RH, Xie SS, Schaefer RF et al (1996) Apoptosis is a major pathway responsible for the resolution of type II pneumocytes in acute lung injury. Am J Pathol 149:845–852PubMedGoogle Scholar
  56. 56.
    Wang HC, Shun CT, Hsu SM et al (2002) Fas/Fas ligand pathway is involved in the resolution of type II pneumocyte hyperplasia after acute lung injury: evidence from a rat model. Crit Care Med 30:1528–1534PubMedCrossRefGoogle Scholar
  57. 57.
    Albertine KH, Soulier MF, Wang Z et al (2002) Fas and fas ligand are up-regulated in pulmonary edema fluid and lung tissue of patients with acute lung injury and the acute respiratory distress syndrome. Am J Pathol 161:1783–1796PubMedGoogle Scholar
  58. 58.
    Sookhai S, Wang JJ, McCourt M et al (2002) A novel therapeutic strategy for attenuating neutrophil-mediated lung injury in vivo. Ann Surg 235:285–291PubMedCrossRefGoogle Scholar
  59. 59.
    Hagimoto N, Kuwano K, Kawasaki M et al (1999) Induction of interleukin-8 secretion and apoptosis in bronchiolar epithelial cells by Fas ligation. Am J Respir Cell Mol Biol 21:436–445PubMedGoogle Scholar

Copyright information

© Springer-Verlag Italia 2006

Authors and Affiliations

  • A. B. Souza-Fernandes
    • 1
  • P. R. M. Rocco
    • 1
  • W. A. Zin
    • 2
  1. 1.Laboratory of Pulmonary Investigation, Carlos Chagas Filho Institute of BiophysicsFederal University of Rio de JaneiroRio de JaneiroBrazil
  2. 2.Laboratory of Respiration Physiology, Carlos Chagas Filho Institute of BiophysicsFederal University of Rio de JaneiroRio de JaneiroBrazil

Personalised recommendations