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Elastase-Induced Lung Emphysema Models in Mice

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Alpha-1 Antitrypsin Deficiency

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1639))

Abstract

Pulmonary emphysema is one of the distinct pathological forms of chronic obstructive pulmonary disease (COPD) that is accompanied by gradual elimination of alveolar tissue, causing reductions in lung recoil and leading to difficulty in breathing. As there is no cure for emphysema, animal models are often used to better understand the pathogenesis and progression of the disease. One widely used animal model of emphysema is the elastase treatment. In this chapter, we describe two methods of elastase-induced emphysema in mice. The first is a single-dose treatment, whereby elastase is introduced oropharengeally into the lung and the structure and/or function of the lungs are studied between 2 days and 4 weeks following the treatment. The second method consists of exposing mice repeatedly (four times) to elastase intratracheally and observing the effects of the treatment 1–4 weeks following the last administration of the enzyme. Both protocols are described in detail, and examples of lung structure and function of the emphysematous mouse lung are provided.

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References

  1. Global strategy for the diagnosis, management and prevention of chronic obstructive pulmonary disease (2013). Accessed Revised 2013

    Google Scholar 

  2. Mathers CD, Loncar D (2006) Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med 3 (11):e442. doi:10.1371/journal.pmed.0030442

  3. Luisetti M, Seersholm N (2004) Alpha1-antitrypsin deficiency. 1: epidemiology of alpha1-antitrypsin deficiency. Thorax 59(2):164–169

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Cantor JO, Cerreta JM, Ochoa M, Ma S, Chow T, Grunig G, Turino GM (2005) Aerosolized hyaluronan limits airspace enlargement in a mouse model of cigarette smoke-induced pulmonary emphysema. Exp Lung Res 31(4):417–430

    Article  CAS  PubMed  Google Scholar 

  5. de Santi MM, Martorana PA, Cavarra E, Lungarella G (1995) Pallid mice with genetic emphysema. Neutrophil elastase burden and elastin loss occur without alteration in the bronchoalveolar lavage cell population. Lab Investig 73(1):40–47

    PubMed  Google Scholar 

  6. Fisk DE, Kuhn C (1976) Emphysema-like changes in the lungs of the blotchy mouse. Am Rev Respir Dis 113(6):787–797

    CAS  PubMed  Google Scholar 

  7. Foronjy RF, Mercer BA, Maxfield MW, Powell CA, D'Armiento J, Okada Y (2005) Structural emphysema does not correlate with lung compliance: lessons from the mouse smoking model. Exp Lung Res 31(6):547–562

    Article  PubMed  Google Scholar 

  8. Gardi C, Martorana PA, Calzoni P, van Even P, de Santi MM, Cavarra E, Lungarella G (1992) Lung collagen synthesis and deposition in tight-skin mice with genetic emphysema. Exp Mol Pathol 56(2):163–172

    Article  CAS  PubMed  Google Scholar 

  9. Hamakawa H, Bartolak-Suki E, Parameswaran H, Majumdar A, Lutchen KR, Suki B (2011) Structure-function relations in an elastase-induced mouse model of emphysema. Am J Respir Cell Mol Biol. doi:10.1165/rcmb.2010-0473OC. 2010-0473OC [pii]

    PubMed  Google Scholar 

  10. Lucattelli M, Cavarra E, de Santi MM, Tetley TD, Martorana PA, Lungarella G (2003) Collagen phagocytosis by lung alveolar macrophages in animal models of emphysema. Eur Respir J 22(5):728–734

    Article  CAS  PubMed  Google Scholar 

  11. O'Donnell MD, O'Connor CM, FitzGerald MX, Lungarella G, Cavarra E, Martorana PA (1999) Ultrastructure of lung elastin and collagen in mouse models of spontaneous emphysema. Matrix Biol 18(4):357–360

    Article  PubMed  Google Scholar 

  12. Shiomi T, Okada Y, Foronjy R, Schiltz J, Jaenish R, Krane S, D'Armiento J (2003) Emphysematous changes are caused by degradation of type III collagen in transgenic mice expressing MMP-1. Exp Lung Res 29(1):1–15

    Article  CAS  PubMed  Google Scholar 

  13. Yao H, Arunachalam G, Hwang JW, Chung S, Sundar IK, Kinnula VL, Crapo JD, Rahman I (2010) Extracellular superoxide dismutase protects against pulmonary emphysema by attenuating oxidative fragmentation of ECM. Proc Natl Acad Sci U S A 107(35):15571–15576. doi:10.1073/pnas.1007625107

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Antunes MA, Abreu SC, Cruz FF, Teixeira AC, Lopes-Pacheco M, Bandeira E, Olsen PC, Diaz BL, Takyia CM, Freitas IP, Rocha NN, Capelozzi VL, Xisto DG, Weiss DJ, Morales MM, Rocco PR (2014) Effects of different mesenchymal stromal cell sources and delivery routes in experimental emphysema. Respir Res 15:118. doi:10.1186/s12931-014-0118-x

    Article  PubMed  PubMed Central  Google Scholar 

  15. Cruz FF, Antunes MA, Abreu SC, Fujisaki LC, Silva JD, Xisto DG, Maron-Gutierrez T, Ornellas DS, Sa VK, Rocha NN, Capelozzi VL, Morales MM, Rocco PR (2012) Protective effects of bone marrow mononuclear cell therapy on lung and heart in an elastase-induced emphysema model. Respir Physiol Neurobiol 182(1):26–36. doi:10.1016/j.resp.2012.01.002

    Article  CAS  PubMed  Google Scholar 

  16. Bracke KR, Dentener MA, Papakonstantinou E, Vernooy JH, Demoor T, Pauwels NS, Cleutjens J, van Suylen RJ, Joos GF, Brusselle GG, Wouters EF (2010) Enhanced deposition of low-molecular-weight hyaluronan in lungs of cigarette smoke-exposed mice. Am J Respir Cell Mol Biol 42(6):753–761. doi:10.1165/rcmb.2008-0424OC

    Article  CAS  PubMed  Google Scholar 

  17. Cavarra E, Bartalesi B, Lucattelli M, Fineschi S, Lunghi B, Gambelli F, Ortiz LA, Martorana PA, Lungarella G (2001) Effects of cigarette smoke in mice with different levels of alpha(1)-proteinase inhibitor and sensitivity to oxidants. Am J Respir Crit Care Med 164(5):886–890. doi:10.1164/ajrccm.164.5.2010032

    Article  CAS  PubMed  Google Scholar 

  18. Hautamaki RD, Kobayashi DK, Senior RM, Shapiro SD (1997) Requirement for macrophage elastase for cigarette smoke-induced emphysema in mice. Science 277(5334):2002–2004

    Article  CAS  PubMed  Google Scholar 

  19. Ofulue AF, Ko M, Abboud RT (1998) Time course of neutrophil and macrophage elastinolytic activities in cigarette smoke-induced emphysema. Am J Phys 275(6 Pt 1):L1134–L1144

    CAS  Google Scholar 

  20. Martorana PA, Brand T, Gardi C, van Even P, de Santi MM, Calzoni P, Marcolongo P, Lungarella G (1993) The pallid mouse. A model of genetic alpha 1-antitrypsin deficiency. Lab Investig 68(2):233–241

    CAS  PubMed  Google Scholar 

  21. Hantos Z, Adamicza A, Janosi TZ, Szabari MV, Tolnai J, Suki B (2008) Lung volumes and respiratory mechanics in elastase-induced emphysema in mice. J Appl Physiol 105(6):1864–1872. doi:10.1152/japplphysiol.90924.2008. 90924.2008 [pii]

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Ito S, Ingenito EP, Brewer KK, Black LD, Parameswaran H, Lutchen KR, Suki B (2005) Mechanics, nonlinearity, and failure strength of lung tissue in a mouse model of emphysema: possible role of collagen remodeling. J Appl Physiol 98:503–511

    Article  PubMed  Google Scholar 

  23. Sawada M, Ohno Y, La BL, Funaguchi N, Asai T, Yuhgetsu H, Takemura G, Minatoguchi S, Fujiwara H, Fujiwara T (2007) The Fas/Fas-ligand pathway does not mediate the apoptosis in elastase-induced emphysema in mice. Exp Lung Res 33(6):277–288. doi:10.1080/01902140701509458

    Article  CAS  PubMed  Google Scholar 

  24. Takahashi A, Majumdar A, Parameswaran H, Bartolak-Suki E, Suki B (2014) Proteoglycans maintain lung stability in an elastase-treated mouse model of emphysema. Am J Respir Cell Mol Biol 51(1):26–33. doi:10.1165/rcmb.2013-0179OC

    Article  PubMed  PubMed Central  Google Scholar 

  25. Parameswaran H, Majumdar A, Ito S, Alencar AM, Suki B (2006) Quantitative characterization of airspace enlargement in emphysema. J Appl Physiol 100(1):186–193

    Article  PubMed  Google Scholar 

  26. Kononov S, Brewer K, Sakai H, Cavalcante FS, Sabayanagam CR, Ingenito EP, Suki B (2001) Roles of mechanical forces and collagen failure in the development of elastase-induced emphysema. Am J Respir Crit Care Med 164(10 Pt 1):1920–1926

    Article  CAS  PubMed  Google Scholar 

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Acknowledgment

B. Suki and E. Bartolák-Suki were supported by the National Institutes of Health Grant HL-111745. P. Rocco was supported by the Brazilian Council for Scientific and Technological Development (CNPq), the Carlos Chagas Filho Rio de Janeiro State Research Foundation (FAPERJ), and the Department of Science and Technology, Brazilian Ministry of Health (DECIT/MS). P. Rocco would like to express her gratitude to Dr. Milena Vasconcellos for help with microscopy.

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Suki, B., Bartolák-Suki, E., Rocco, P.R.M. (2017). Elastase-Induced Lung Emphysema Models in Mice. In: Borel, F., Mueller, C. (eds) Alpha-1 Antitrypsin Deficiency . Methods in Molecular Biology, vol 1639. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7163-3_7

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  • DOI: https://doi.org/10.1007/978-1-4939-7163-3_7

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-7161-9

  • Online ISBN: 978-1-4939-7163-3

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