, Volume 171, Issue 6, pp 335–344 | Cite as

Growth factors accelerate epithelial repair in sheep trachea

  • Robert E. Barrow
  • Cheng-Z Wang
  • Michael J. Evans
  • David N. Herndon


Toxic gases and fumes have been shown to be injurious to the upper airways. Repair of this injury involves proliferation and migration of surviving nonciliated cells, followed by differentiation to a normal phenotype. Because recent results suggested that growth factors could improve the outcome of an airway injury, we undertook this study to determine the efficacy of these materials as an initial treatment to accelerate the healing process. In 24 anesthetized sheep, a portion of the trachea was exposed to smoke from smouldering cotton cooled to 37°C. Twelve received aerosolized epidermal growth factor plus platelet derived growth factor, while twelve received placebo. At 10 days after injury, nonciliated and ciliated cells were totally absent in the injured trachea receiving the placebo. In animals receiving growth factors, nonciliated and ciliated cells, however, were present (56% and 31% of uninjured trachea, respectively). At 13 days after injury, nonciliated and ciliated cell counts in those receiving placebo were 67% and 33% of uninjured, respectively. In sheep receiving growth factors, tracheal nonciliated and ciliated cell counts had increased to 105% and 64% of uninjured trachea, respectively. We conclude that growth factors therapy after airway injury stimulates cell proliferation and differentiation, and this therapeutic intervention to accelerate the repair process in acute airway injury is an approach applicable to humans.

Key words

Epidermal growth factor Platelet derived growth factor Inhalation injury Tracheal repair process 


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  1. 1.
    Barrow RE, Morris SE, Bsadre JO, Herndon DN (1990) Selective permeability changes in the lungs and airways of sheep after toxic smoke inhalation. J Appl Physiol 68:2165–2170Google Scholar
  2. 2.
    Barrow RE, Morris SE, Linares HA, Herndon DN (1991) Tracheal venous blood and lymph collection: a model to study airway injury in sheep. J Appl Physiol 70(4):1645–1649Google Scholar
  3. 3.
    Barrow RE, Wang CZ, Cox RA, Evans MJ (1992) Cellular sequence of tracheal repair in sheep after smoke inhalation injury. Lung 170:331–338Google Scholar
  4. 4.
    Carpenter G, Cohen S (1979) Epidermal growth factor. Ann Rev Biochem 48:193–216Google Scholar
  5. 5.
    Deuel TF, Senior RM, Huang JS, Griffin GL (1982) Chemotaxis of monocytes and neutrophils to platelet-derived growth factor. J Clin Invest 69:1046–1049Google Scholar
  6. 6.
    Evans MJ, Shami SG Lung cell kinetics. In: Parent RA (ed) Lung cell biology (Lung Biology in Health and Disease, vol. 1) Marcel Dekker, Inc., New York, pp. 145–155Google Scholar
  7. 7.
    Holtzmann MJ, Fabbri LM, O'Bryne PM (1983) Importance of airway inflammation for hyper-responsiveness induced by ozone. Am Rev Respir Dis 127:686–690Google Scholar
  8. 8.
    Jetten AM (1991) Growth and differentiation factors in tracheobronchial epithelium. Am J Physiol 260:L361-L373Google Scholar
  9. 9.
    Kilburn KH, McKenzie WN, Thurston RJ (1975) Cellular effects of cigarette smoke on hamster airways. Chest 67:54S-55SGoogle Scholar
  10. 10.
    Man SP, Hubert WC (1988) Airway repair and adaptation to inhalation injury. In: Loke J (ed) Pathophysiology and treatment of inhalation injury. Marcel Dekker Inc., New York, pp. 1–47Google Scholar
  11. 11.
    Pierce GF, Mustoe TA, Lingelbach J, Masakowski VR, Gramates P, Deuel TF (1989) Transforming growth factor β reverses the glucocorticoid-induced wound-healing deficit in rats. Possible regulation in macrophages by platelet-derived growth factor. Proc Natl Acad Sci 86:2229–2233Google Scholar
  12. 12.
    Pledger WJ, Stiles CD, Antoniades HN, Scher CD (1978) An ordered sequence of events is required before BALB/c-3T3 cells become committed to DNA synthesis. Proc Natl Acad Sci USA 75:2839–2843Google Scholar
  13. 13.
    Ross R, Glomset B, Karija B, Harker L (1974) A platelet-dependent serum factor that stimulates the proliferation of arterial smooth muscle cells in vitro. Proc Natl Acad Sci USA 71:1207–1210Google Scholar
  14. 14.
    Shipley GD, Childs CB, Volkenant ME, Moses HL (1984) Differential effects of epidermal growth factor, transforming growth factor, and insulin on DNA and protein synthesis and morphology in serum-free cultures of AKR-2B cells. Cancer Res 44:710–716Google Scholar
  15. 15.
    Stahlman MT, Gray ME, Chytil F, Sundell H (1988) Effect of retinol on fetal lamb tracheal epithelium, with and without epidermal growth factor. Lab Invest 59:25–35Google Scholar
  16. 16.
    Wang CZ, Evans MJ, Cox RA, Burke AS, Zhu QY, Herndon DN, Barrow RE (1992) Morphologic changes in basal cells during repair of tracheal epithelium. Amer J Pathol 141(3):753–759Google Scholar

Copyright information

© Springer-Verlag New York Inc 1993

Authors and Affiliations

  • Robert E. Barrow
    • 1
  • Cheng-Z Wang
    • 1
  • Michael J. Evans
    • 1
  • David N. Herndon
    • 1
  1. 1.Shriners Burns Institute and Departments of Surgery, Physiology and Biophysics, Anatomy & NeurosciencesUniversity of Texas Medical BranchGalvestonUSA

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