Skip to main content
Log in

Growth factors accelerate epithelial repair in sheep trachea

  • Published:
Lung Aims and scope Submit manuscript

Abstract

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.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  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 68:2165–2170

    Google Scholar 

  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):1645–1649

    Google Scholar 

  3. Barrow RE, Wang CZ, Cox RA, Evans MJ (1992) Cellular sequence of tracheal repair in sheep after smoke inhalation injury. Lung 170:331–338

    Google Scholar 

  4. Carpenter G, Cohen S (1979) Epidermal growth factor. Ann Rev Biochem 48:193–216

    Google Scholar 

  5. Deuel TF, Senior RM, Huang JS, Griffin GL (1982) Chemotaxis of monocytes and neutrophils to platelet-derived growth factor. J Clin Invest 69:1046–1049

    Google Scholar 

  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. 145–155

  7. Holtzmann MJ, Fabbri LM, O'Bryne PM (1983) Importance of airway inflammation for hyper-responsiveness induced by ozone. Am Rev Respir Dis 127:686–690

    Google Scholar 

  8. Jetten AM (1991) Growth and differentiation factors in tracheobronchial epithelium. Am J Physiol 260:L361-L373

    Google Scholar 

  9. Kilburn KH, McKenzie WN, Thurston RJ (1975) Cellular effects of cigarette smoke on hamster airways. Chest 67:54S-55S

    Google Scholar 

  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. 1–47

    Google Scholar 

  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 86:2229–2233

    Google Scholar 

  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 75:2839–2843

    Google Scholar 

  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 71:1207–1210

    Google Scholar 

  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 44:710–716

    Google Scholar 

  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 59:25–35

    Google Scholar 

  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):753–759

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

Offprint requests to: R. E. Barrow

Rights and permissions

Reprints and permissions

About this article

Cite this article

Barrow, R.E., Wang, CZ., Evans, M.J. et al. Growth factors accelerate epithelial repair in sheep trachea. Lung 171, 335–344 (1993). https://doi.org/10.1007/BF00165699

Download citation

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00165699

Key words

Navigation