Elastin and the Lung

  • J. M. Davidson
Part of the Current Topics in Rehabilitation book series (CURRENT REHAB)


Elastin, a rubbery, fibrous connective tissue protein, plays several critical roles in the biomechanics of the lung and its associated vasculature. It is the principal component of the elastic fibre, which is a composite of the amorphous elastic protein and one or more microfibrillar components. Elastic fibres provide resiliency to numerous pulmonary structures including the alveolar wall, the bronchiolar interstitium, the medial layers of arterial and venous elements, lymphatics, and the pleura. The unusual hydrophobic properties of the protein, together with the presence of numerous intermolecular crosslinks, in particular desmosine and isodesmosine, produce a highly insoluble, durable network of polypeptide chains that function as a perfect elastomer in an aqueous environment.


Epithelial Line Fluid Pulmonary Emphysema Lysyl Oxidase Emphysematous Lung Cutis Laxa 
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  1. 1.
    Uitto J., Olsen D.R., Fazio M.J., Rosenbloom J.: Molecular pathology of elastin. In: Tamburro A.M., Davidson J.M. (Eds.) Elastin: Chemical and Biological Aspects. Galatina, Congedo Editore, 1990; 305–330Google Scholar
  2. 2.
    Ledoux-Corbusier M.: Cutis laxa: congenital form with pulmonary emphysema. An ultrastructural study. J. Cutan. Pathol. 1983; 10: 340–349PubMedCrossRefGoogle Scholar
  3. 3.
    Sephel G.C., Byers P.H., Holbrook K.A., Davidson J.M.: Heterogeneity of elastin expression in cutis laxa fibroblast strains. J. Invest. Dermatol. 1989; 93: 147–153PubMedCrossRefGoogle Scholar
  4. 4.
    Olsen D.A., Fazio M.J., Shamban A.T., Rosenbloom J., Uitto J.: Cutis laxa-reduced elastin gene expression in skin fibroblast cultures as determined by hybridization with a homologous cDNA and an exon 1-specific oligonucleotide. J. Biol. Chem. 1988; 263: 6465–6468PubMedGoogle Scholar
  5. 5.
    Soskel N.T., Sandberg L.B.: Pulmonary emphysema. From animal models to human diseases. In: Uitto J., Perejda A., (Eds.) Connective Tissue Disease, New York, Marcel Dekker, 1986; 423–453Google Scholar
  6. 6.
    Janoff A.: Elastase in tissue injury. Annu. Rev. Med. 1985; 36: 207–216PubMedCrossRefGoogle Scholar
  7. 7.
    Bashir M., Indih Z., Yeh H., Abrams W., Ornstein-Goldstein N., Rosenbloom J.C., Fazio M., Uitto J., Mecham R., Rosenbloom J.: Elastin gene structure and mRNA alternative splicing. In: TamburroA.M., DavidsonJ.M. (Eds.)Elastin: ChemicalandBiologicalAspects, Galatina, Congedo Editore 1990; 45–70Google Scholar
  8. 8.
    Urry D.W.: Entropic elastic processes in protein mechanisms. I. Elastic structure due to an inverse temperature transition and elasticity due to internal chain dynamics. J. Protein. Chem. 1988; 7: 1–34Google Scholar
  9. 9.
    Gosline J.M.: Hydrophobic interaction and a model for the elasticity of elastin. Biopolymers 1978; 17: 677–695PubMedCrossRefGoogle Scholar
  10. 10.
    Kagan H.M.: Characterization and regulation of lysyl oxidase. In: Mecham R.P., (Ed.) Regulation of Matrix Accumulation New York, Academic Press., 1986; 322–399Google Scholar
  11. 11.
    Starcher B.C.: Elastin and the lung. Thorax 1986; 41: 577–585PubMedCrossRefGoogle Scholar
  12. 12.
    Davidson J.M., Berg R.A.: Posttransational events in collagen biosynthesis. In: Hand A., Oliver C. (Eds.) Meth. Cell Biol. New York, Academic Press 1981; 119–136Google Scholar
  13. 13.
    Ellis R.J., van der Vies S.M., Hemmingsen S.M.: The molecular chaperone concept. Biochem. Soc. Symp. 1989; 55: 145–153PubMedGoogle Scholar
  14. 14.
    Davidson J.M., Giro M.G., Sutcliffe M., Zoia O., Quaglino Jr. D., Liu J.M., Perkett E., Meyrick B., Broadley K.M., Russel S., Sephel G.C.: Regulation of elastin synthesis. In: Tamburro A.M., Davidson J.M. (Eds.) Elastin: Chemical and Biological Aspects, Galatina, Congedo Editore 1990; 393–405Google Scholar
  15. 15.
    De Clerck Y.A., Jones P.A.: The effect of ascorbic acid on the nature an a production of collagen and elastin by rat smooth muscle cells. Biochem J. 1986: 217–225Google Scholar
  16. 16.
    Dunn D.M., Franzblau C.: Effects of ascorbate on insoluble elastin accumulation and crosslink formation in rabbit pulmonary artery smooth muscle cell cultures. Biochemistry 1983; 21: 4195–4202CrossRefGoogle Scholar
  17. 17.
    Indik Z., Yeh H., Ornstein-Goldstein N., Sheppard P., Anderson N., Rosenbloom J.C., Peltoman L., Rosenbloom J.: Alternative splicing of human elastin mRNA indicated by sequence analysis of cloned genomic and complementary DNA. Proc. Natl. Acad. Sci. USA 1987; 84: 5680–5684PubMedCrossRefGoogle Scholar
  18. 18.
    Fazio M.J., Mattei M.G., Chu M.L., Black D., Solomon E., Davidson J.M., Uitto J.: Human elastin gene: Chromosomal mapping to locus 7g11.2. Am. J. Hum. Genet. 1991; 48: 696–703PubMedGoogle Scholar
  19. 19.
    Raju K., Anwar R.A.: Primary structures of bovine elastin a,b, and c deduced from the sequences of cDNA clones. J. Biol. Chem. 1987; 262: 5755–5762PubMedGoogle Scholar
  20. 20.
    Pollock J., Baule V.J., Rich C.B., Ginsburg C.D., Curtis S., Foster J.A.: Chick tropoelastin isoforms. From the gene to the extracellular matrix. J. Biol. Chem. 1990; 265: 3697–3702PubMedGoogle Scholar
  21. 21.
    Wreen D.S., Parks W.C., Whitehouse L.A., Crouch E.C., Kinich U., Rosenbloom J., Mecham R.P.: Identification of multiple tropoelastins secreted by bovine cells. J. Biol. Chem. 1987; 262: 2244–2249Google Scholar
  22. 22.
    Fazio M.J., Kahari V.M., Bashir M.M., Saitla B., Rosenbloom J., Uitto J.: Regulation of elastin gene expression: evidence for functional promoter activity in the 5-flanking region of the human gene. J. Invest. Dermatol. 1990; 94: 181–196CrossRefGoogle Scholar
  23. 23.
    Cleary E.G.: The microfibrillar component of the elastic fibers. Morphology and Biochemistry. In: Uitto J., Perejda A. (Eds.) Connective Tissue Disease. New York, Marcel Dekker 1986; 55–81Google Scholar
  24. 24.
    Ross R., Bornstein P.: Elastic fibers in the body. Sci. Am. 1971; 224: 44–52PubMedGoogle Scholar
  25. 25.
    Sakai L.Y., Keene D.R., Engvall E.: Fibrillin, a new 350kD glycoprotein, is a component of extracellular microfibrils. J. Cell. Biol. 1986; 103: 2499–2509PubMedCrossRefGoogle Scholar
  26. 26.
    Maddox B.K., Sakai L.Y., Keene D.R., Glanville R.W.: Connective tissue microfibrils. Isolation and characterization of three large pepsin-resistant domains of fibrillin. J. Biol. Chem. 1989; 264: 21381–21385PubMedGoogle Scholar
  27. 27.
    Gibson M.A., Kumaratilake J.S., Cleary E.G.: The protein components of the 12-nanometer microfibrils of elastic and nonelastic tissue. J. Biol. Chem. 1989; 264: 4590–4598PubMedGoogle Scholar
  28. 28.
    Hollister D.W., Godfrey M., Sakai L.Y., Pyeritz R.E.: Immunohistologic abnormalities of the microfibrillar-fiber system in the Marfan syndrome. N. Engl. J. Med. 1990; 32: 152–159CrossRefGoogle Scholar
  29. 29.
    Hinek A., Wrenn D.S., Mecham R.P., Barondes S.H.: The elastin receptor, a galactoside-binding protein. Science 1988; 239: 1539–1541PubMedCrossRefGoogle Scholar
  30. 30.
    Mecham R P, Hinek A., Entwistle R., Wrenn D.S., Griffin G.L., Senior R.M.: Elastin binds to a multifunctional 97-Kilodalton peripheral membrane protein. Biochemistry 1989; 28: 3716–3722PubMedCrossRefGoogle Scholar
  31. 31.
    Mecham R.P., Hinek A., Griffin G.L., Senior R.M., Liotta L.A.: The elastin receptor shows structural and functional similarities to the 67-kDa tumor cell laminin receptor. J. Biol. Chem. 1989; 264: 16652–16657PubMedGoogle Scholar
  32. 32.
    Blood C.H., Sasse J., Brodt P., Zetter B.R.: Identification of a tumor cell receptor for VGVAPG, an elastin-derived chemotactic peptide. J. Cell. Biol. 1988; 107: 1987–1993PubMedCrossRefGoogle Scholar
  33. 33.
    Netland P.A., Zetter B.R.: Melanoma cell adhesion to defined extracellular matrix components. Biochem. Biophys. Res. Commun. 1986; 139: 515–522PubMedCrossRefGoogle Scholar
  34. 34.
    Hunninghake G.W., Davidson J.M., Rennard S.I., Szapiel S., Gadek J., Crystal R.G.: Mechanisms of pulmonary emphysema. Attraction of macrophage precursors to sites of disease activity by elastin fragments. Science, 1981; 212: 925–927PubMedCrossRefGoogle Scholar
  35. 35.
    Tobias J.W., Bern M.M., Netland P.A., Zetter B.R.: Monocyte adhesion to subendothelial components. Blood 1987; 69: 1265–1268PubMedGoogle Scholar
  36. 36.
    Senior R.M., Hinek A., Griffin G.L., Pipoly D.J., Crouch E.C., Mecham R.P.: Neutrophils show chemotaxis to type IV collagen and its 7S domain and contain a 67 kD type IV collagen binding protein with lectin properties. Am. J. Respir. Cell Mol. Biol. 1989; 1: 479–487PubMedCrossRefGoogle Scholar
  37. 37.
    Cerra R.F., Haywood Reed P.L., Barondes S.H.: Endogenous mammalian lectin localized extracellularly in lung elastic fibers. J. Cell. Biol. 1984; 98: 1580–1589PubMedCrossRefGoogle Scholar
  38. 38.
    Powell J.T.: Evidence against lung galaptin being important to the synthesis or organization of the elastic fibril. Biochem. J. 1988; 252: 447–452PubMedGoogle Scholar
  39. 39.
    Hornebeck W., Tixier J.M., Robert L.: Inducible adhesion of mesenchymal cells to elastic fibers. Proc. Natl. Acad. Sci. USA, 1986; 83: 5517–5520PubMedCrossRefGoogle Scholar
  40. 40.
    Robert L. Jacob M.P., Fulop T., Timar J., Hornebeck W.: Elastonectin in the elastin receptor. Pathol. Biol. (Paris) 1989; 37: 736–741Google Scholar
  41. 41.
    Clark J.M., Glagov S.: Transmural organization of the arterial media. The lamellar unit revisited. Arteriosclerosis 1985; 5: 19–34PubMedCrossRefGoogle Scholar
  42. 42.
    Shibahara S., Davidson J.M., Smith K., Crystal R.O.: Modulation of elastin synthesis and mRNA activity in developing sheep lung. Biochemistry 1981; 20: 6577–6584PubMedCrossRefGoogle Scholar
  43. 43.
    Myers B., DubickM., Last J.A., Rucker R.B.: Elastin synthesis during perinatal lung development in the rat. Biochim Biophys. Acta 1983; 761: 17–22Google Scholar
  44. 44.
    Lefevre M., Rucker R.B.: Aorta elastin turnover in normal and hypercholesterolemic Japanese quail. Biochim. Biophys. Acta 1980; 630: 519–529PubMedCrossRefGoogle Scholar
  45. 45.
    Christie R.: The elastic properties of the emphysematous lung and their clinical significance. J. Clin. Invest. 1934; 13: 295–297PubMedCrossRefGoogle Scholar
  46. 46.
    Laurell C.N., Eriksson S.: The electrophoretic al-globulin pattern of serum in al-antitrypsin deficiency. Scand. J. Clin. Lab. Invest. 1963; 15: 132–140Google Scholar
  47. 47.
    Kuhn C., Senior R.M.: The role of elastases in the development of emphysema. Lung. 1978; 155: 185–197PubMedCrossRefGoogle Scholar
  48. 48.
    Pierce J.A., Hocott J.B., Ebert R.V.: The collagen and elastin content of the lung in emphysema. Ann. Intern. Med. 1961; 55: 210–222PubMedCrossRefGoogle Scholar
  49. 49.
    Meyrick B., Reid L.M.:In: Hodson W.A. (Ed.) Development of the Lung. New York, Marcel Dekker, 1977; 135–214Google Scholar
  50. 50.
    Quaglino Jr D., Nanney L.B., Kennedy R., Davidson J.M.: Localized effects of transforming growth factor-13 on extracellular matrix gene expression during wound healing. I. Excisional wound model. Lab. Invest. 1990; 63: 307–319PubMedGoogle Scholar
  51. 51.
    Davidson J.M., Giro M.G.: Repair of elastic tissue. In: Cohen I.K., Digelmann R., Lindblad W. (Eds.) Wound Repair, 3rd ed. New York, Saunders, 1991Google Scholar
  52. 52.
    Perkett E.A., Brigham L.K., Meyrick B.: Continuous air embolization into sheep causes sustained pulmonary hypertension and increased vascular reactivity. Am. J. Path. 1988; 123: 444–454Google Scholar
  53. 53.
    Mecham R.P., Withehouse L.A., Wrenn D.S., Parks W.C., Griffin G.L., Senior R.M., Crouch E.C., Stenmark K.R., Voelkel N.F.: Smooth muscle-mediated connective tissue remodeling in pulmonary hypertension. Science 1987; 237: 423–426PubMedCrossRefGoogle Scholar
  54. 54.
    Prosser I.W.; Stenmark K.R., Suthar M., Crouch E.C., Mecham R.P., Parks W.C.: Regional heterogeneity of elastin and collagen gene expression in intralobar arteries in response to hypoxic pulmonary hypertension as demonstrated by in situ hybridization. Am. J. Path. 1989;135:10731087Google Scholar
  55. 55.
    Liu J.M., Davidson J.M.: The elastogenic effect of recombinant transforming growth factor-13 on porcine aortic smooth muscle cells. Biochem. Biophys. Res. Commun. 1988; 154: 895–901PubMedCrossRefGoogle Scholar
  56. 56.
    Roberts A.B., Flanders K.C., Kondaiah P., Thompson N.I., Van Obberghen-Schilling E., Wakefield L., Rossi P., de Crombrugghe B., Heine U., Sporn M.B.: Transforming growth factor-13, biochemistry and roles in embryogenesis, tissue repair and remodeling, and carcinogenesis. Rec. Prog. Horm. Res. 1988; 44: 157–197PubMedGoogle Scholar
  57. 57.
    Yamauchi K., Martinet Y., Basset P., Fells G.S., Crystal R.G.: High levels of transforming growth factor-(3 are present in the epithelial lining fluid of the normal human respiratory tract. Am. Rev. Resp. Dis. 1988; 137: 1360–1363PubMedCrossRefGoogle Scholar
  58. 58.
    Perkett E.A., Lyons R.M., Moses H.L., Brigham K.L., Meyrick B.: Transforming growth factor-13 activity in sheep lung lymph during development of pulmonary hypertension. J. Clin. Invest., 1990, 86, 1459–1464PubMedCrossRefGoogle Scholar
  59. 59.
    Perkett E.A.: Personal communication Google Scholar
  60. 60.
    Foster J., Rich C.B., Florini J.R.: Insulin-like growth factor, somatomedin C, induces the synthesis of elastin in aortic tissue. Coll. Rel. Res. 1987; 7: 161–169CrossRefGoogle Scholar
  61. 61.
    Badesch D.B., Lee P.D., Parks W.C., Stenmark K.R.: Insulin-like growth factor I stimulates elastin synthesis by bovine pulmonary arterial smooth muscle cells. Biochem Biophys. Res. Commun. 1989; 160: 382–397Google Scholar
  62. 62.
    Foster J.A., Miller M.L., Benedict M.R., Richmann R.A., Rich C.B.: Evidence for insulin-like growth factor regulation of chick aortic elastogenesis. Matrix 1989; 9: 328–335PubMedCrossRefGoogle Scholar
  63. 63.
    Rom W.N., Basset P., Fells G.A., Nukiwa T., Trapnell B.C., Crystal R.G.: Alveolar macrophages release an insulin-like growth factor-I-type molecule. J. Clin. Invest. 1988; 82: 1685–1693PubMedCrossRefGoogle Scholar
  64. 64.
    Trackman P.C., Pratt A.M., Wolanski A., Tang S.S., Offner G.D., Troxler R.F., Kagan H.M.: Cloning of rat aorta lysyl oxidase cDNA: Complete codons and predicted amino acid sequence. Biochemistry 1990; 29: 4863–4870PubMedCrossRefGoogle Scholar
  65. 65.
    King G.S., Starcher B.C., Kuhn C.T.: The measurement of elastin turnover by the radioimmunoassay of urinary desmosine excretion. Bull. Eur. Physiopathol. Respir. 1980; 16 (suppl): 61–64PubMedGoogle Scholar
  66. 66.
    Pelham F., Wewers M., Crystal R., Buist A.S., Janoff A.: Urinary excretion of desmosine (elastin cross-links) in subjects with PiZZ al-antitrypsin deficiency, a phenotype associated with hereditary disposition to pulmonary emphysema. Am. Rev. Respir. Dis. 1985; 132: 821–823PubMedGoogle Scholar
  67. 67.
    Schriver E.E., Bernard G.R., Swindell B.B., Sutcliffe M.S., Davidson J.M.: Elastin fragment levels in human plasma, urine, and bronchoalveolar lavage fluid. (BALF) Chest 1989; 96: 1535Google Scholar
  68. 68.
    Perkett E.A., Davidson J.M., Curtis-Atchley P., Sutcliffe M.C., Brigham K.L., Meyrick B.: Lung lymph elastin concentration is increased in sheep with pulmonary hypertension secondary to air embolization. Am. Rev. Respir. Dis. 1989; 139: A174Google Scholar
  69. 69.
    Gadek J.W., Hunninghake G.W., Fells G.A., Zimmerman R.L., Keogh B.A., Crystal R.G.: Evaluation of the protease-antiprotease theory of human destructive lung disease. Bull. Eur. Physiopath. Resp. 1980; 16 (Suppl): 27–40Google Scholar
  70. 70.
    Davidson J.M., Zoia O., Nair R., Meyrick B., Perkett E.A.: unpublished studies Google Scholar
  71. 71.
    Davidson J.M., Giro M.G.: Control of elastin synthesis: Molecular and cellular aspects. In: Mecham R.P. (Ed.) Regulation of Matrix Accumulation. New York, Academic Press, 1986;177216Google Scholar
  72. 72.
    Davidson J.M.: Biochemistry and turnover of lung interstitium. Eur. Resp. J. 1990; 3: 1048–1068Google Scholar

Copyright information

© Springer-Verlag London 1992

Authors and Affiliations

  • J. M. Davidson
    • 1
  1. 1.Research Service, Department of Veterans Affairs Medical Center and Department of PathologyVanderbilt University School of MedicineNashvilleUSA

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