Regeneration of hamster tracheal epithelium after mechanical injury

I. Focal lesions: Quantitative morphologic study of cell proliferation
  • Kevin P. Keenan
  • John W. Combs
  • Elizabeth M. McDowell


All stages of epithelial regeneration following a focal denuding mechanical injury have been quantified in hamster trachea. The epithelium was divided into wound and non-wound sites and every cell around the entire tracheal circumference was counted and catergorized according to cell type. The control hamster tracheal epithelium was composed of about 33% ciliated cells, 57% secretory cells and 10% basal cells. Proliferative activity, measured as mitotic rate (MR) following a 6 h colchicine metaphase blockade, was low and confined to the secretory and basal cells. The total cell population had a MR of 0.12% (0.08% secretory cells; 0.04% basal cells).

Following a focal denuding wound in the ventral portion of the epithelium, 18% of all the epithelial cells were lost by 6 h. This loss increased to 31% by 12 h. Secretory cells and basal cells from the adjacent non-wounded epithelium flattened into a squamous morphology and during the first 12 h migrated into the wound at about 0.5 μ per min to cover the defect. Cell division at the wound was low at 12 h (MR = 0.4%), but by 24 h an exponential increase in cell proliferation had occured in the wound site (MR = 31.1%). Secretory cells (MR = 19.9%), basal cells (MR = 1.4%) and squamous cells-a mixture of flattened secretory and basal cells (MR = 9.8%)-contributed to this proliferative activity. Mitotic activity in the non-wounded epithelium remained low (MR= 0.6%).

Cell proliferation at the wound site produced a multilayered epidermoid metaplastic epithelium by 36 and 48 h. Mitotic activity remained high at these times (36 h MR = 21%, 48 h MR = 12%). Thereafter (60 h–120 h) mitotic activity fell to near control levels, and the wound epithelium was gradually replaced by recognizable basal, secretory and preciliated cells. The latter, first seen in the wound at 48 h, and recognized as very large pale non-ciliated cells, developed cilia through 60, 72, and 96 h so that a nearly normal epithelium was restored by 120 h.

Key words

Trachea Hamster Regeneration Mechanical injury 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Adamson IYR, Bowden DH (1974) The type 2 cell as progenitor of alveolar epithelial regeneration: A cytodynamic study in mice after exposure to oxygen. Lab Invest 30:35–42PubMedGoogle Scholar
  2. Bang FB, Bang BG (1977) Mucous membrane injury and repair. In: Brain JD, Proctor DF, Reid LM (eds) Respiratory defense mechanisms, part I. Marcel Dekker, New York, pp 453–488Google Scholar
  3. Bang FB, Foard M, Bang BG (1974) Acute Newcastle viral infection of the upper respiratory tract of the chicken I. A model for the study of environmental factors on upper respiratory tract infection. Am J Pathol 76:333–348PubMedCentralPubMedGoogle Scholar
  4. Becci PJ, McDowell EM, Trump BF (1978a) The respiratory epithelium II. Hamster trachea, bronchus and bronchioles. J Natl Cancer Inst 61:551–561PubMedGoogle Scholar
  5. Becci PJ, McDowell EM, Trump BF (1978b) The respiratory epithelium IV. Histogenesis of epidermoid metaplasia and carcinomain situ in the hamster. J Natl Cancer Inst 61:577–586PubMedGoogle Scholar
  6. Bils RF, Christie BR (1980) The experimental pathology of oxidant and air pollutant inhalation. Int Rev Exp Pathol 21:195–293PubMedGoogle Scholar
  7. Bindreiter M, Schuppler J, Stockinger L (1968) Zeilproliferation und Differenzierung im Trachealepithel der Ratte. Exp Cell Res 50:377–382CrossRefGoogle Scholar
  8. Boren HG, Paradise LJ (1978) Cytokinetics of lung. In: Harris CC (ed) Pathogenesis and therapy of lung cancer. Marcel Dekker, New York, pp 369–418Google Scholar
  9. Boren HG, Pauley J, Wright EC, Kaufman DG, Smith JM, Harris CC (1974) Cell populations in the hamster tracheal epithelium in relation to vitamin A status. Int J Vit Nutr Res 44:383–390Google Scholar
  10. Castleman WL, Dungworth DL, Schwartz LW, Tyler WS (1980) Acute respiratory bronchiolitis. An ultrastructural and autoradiographic study of epithelial cell injury and renewal in Rhesus monkeys exposed to ozone. Am J Pathol 98:811–840PubMedCentralPubMedGoogle Scholar
  11. Chakrin LW, Saunders LZ (1974) Experimental chronic bronchitis. Pathology in the dog. Lab Invest 30:145–154PubMedGoogle Scholar
  12. Clyde WA (1980) Experimental models for study of common respiratory viruses. Envir Health Persp 35:107–112CrossRefGoogle Scholar
  13. Condon WB (1942) Regeneration of tracheal and bronchial epithelium. J Thorac Surg 11:333–346Google Scholar
  14. Correll NO, Beattie EH (1956) The characteristics of regeneration of respiratory epithelium. Surg Gynecol Obstet 103:209–211PubMedGoogle Scholar
  15. Cuppage FE, Chiga M, Tate A (1972) Cell cycle studies in the regenerating rat nephron following injury with mercuric chloride. Lab Invest 26:122–126PubMedGoogle Scholar
  16. Dahlgren SE, Dalen H, Dalhamn T (1972) Ultrastructural observations on chemically inducted inflammation in guinea pig trachea. Virchows Arch [Zell Pathol] 11:211–223Google Scholar
  17. Dipasquale A (1975a) Locomotory activity of epithelial cells in culture. Exp Cell Res 94:191–215CrossRefPubMedGoogle Scholar
  18. Dipasquale A (1975 b) Locomotion of epithelial cells. Factor involved in extension of the leading edge. Exp Cell Res 95:425–439Google Scholar
  19. Evans MJ, Johnson LV, Stephens RJ, Freeman G (1976) Renewal of the terminal bronchiolar epithelium in the rat following exposure to NO2 or O3. Lab Invest 35:246–257PubMedGoogle Scholar
  20. Francis T, Stuart-Harris CH (1938) Studies on the nasal histology of epidemic influenza virus infection in the ferret. I. The development and repair of the nasal lesion. J Exp Med 68:789–802PubMedGoogle Scholar
  21. Fleischmann W, Russel O, Fleischmann S (1962) LD 50 and minimal effective anti-mitotic dose of colchicine in various rodents. Med Exp 6:101–104PubMedGoogle Scholar
  22. Gordon RE, Lane BP (1976) Regeneration of rat tracheal epithelium after mechanical injury. II. Restoration of surface integrity during the early hours after injury. Am Rev Resp Dis 113:799–807PubMedGoogle Scholar
  23. Gordon RE, Lane BP (1977) Cytokinetics of rat tracheal epithelium stimulated by mechanical trauma. Cell Tissue Kinet 10:171–181PubMedGoogle Scholar
  24. Gordon RE, Lane BP (1980) Wound repair in rat tracheal epithelium. Division of G1 and G2 arrested cells following injury. Lab Invest 42:616–621PubMedGoogle Scholar
  25. Greenburg SD, Willms RK (1962) Regeneration of respiratory epithelium. An experimental study in dogs. Arch Pathol 73:67–70Google Scholar
  26. Harris CC, Kaufman DG, Sporn MB, Smith JM, Jackson F, Saffiotti U (1973a) Ultrastructural effects of N-methyl-N-nitrosourea on the tracheobronchial epithelium of the Syrian golden hamster. Int J Cancer 12:259–269CrossRefPubMedGoogle Scholar
  27. Harris CC, Silverman T, Smith JM, Jackson E, Boren HG (1973b) Proliferation of tracheal epithelial cells in normal and vitamin A deficient Syrian golden hamsters. J Natl Cancer Inst 51:1059–1062PubMedGoogle Scholar
  28. Harris CC, Frank A, Barrett LA, McDowell EM, Trump BF, Paradise LJ, Boren H (1975) Cytokinetics in the respiratory epithelium of the hamster, cow and man. J Cell Biol 67:158aGoogle Scholar
  29. Hattum AH, James J, Klopper PJ, Muller JH (1979) A model for the study of epithelial migration in wound healing. Virchows Arch [Cell Pathol] 30:221–230Google Scholar
  30. Hilding AC (1965) Regeneration of respiratory epithelium after minimal surface trauma. Ann Otol Rhinol Laryngol 74:903–914CrossRefPubMedGoogle Scholar
  31. Hilding DA, Hilding AC (1966) Ultrastructure of tracheal cilia and cells during regeneration. Ann Otol Rhinol Laryngol 75:281–294CrossRefGoogle Scholar
  32. Jeffery PK, Reid LM (1981) The effect of tobacco smoke, with or without phenylmethyloxadiazole (PMO), on rat bronchial epithelium: A light and electron microscopic study. J Pathol 133:341–359CrossRefPubMedGoogle Scholar
  33. Kauffman SL (1980) Cell proliferation in the mammalian lung. Int Rev Exp Pathol 22:131–191PubMedGoogle Scholar
  34. Kaufman DG, Baker MS, Harris CC, Smith JM, Boren H, Sporn MB, Saffiotti U (1972) Coordinated biochemical and morphologic examination of hamster tracheal epithelium. J Natl Cancer Inst 49:784–792Google Scholar
  35. Keenan KP, Combs JW, McDowell EM (1982b) Regeneration of hamster tracheal epithelium after mechanical injury. II. Multifocal lesions: Stathmokinetic and autoradiographic studies of cell proliferation. Virchows Arch [Cell Pathol] 41:215–229CrossRefGoogle Scholar
  36. Keenan KP, Combs JW, McDowell EM (1982c) Regeneration of hamster tracheal epithelium after mechanical injury. III. Large and small lesions: Comparative stathmokinetic and single pulse and continuous thymidine labeling autoradiographic studies. Virchows Arch [Cell Pathol] 41:231–252CrossRefGoogle Scholar
  37. Keenan KP, Wilson TS, McDowell EM (1982d) Regeneration of hamster tracheal epithelium after mechanical injury. IV. Histochemical, immunocytochemical and ultrastructural studies. Submitted to Virchows Arch [Cell Pathol]Google Scholar
  38. Kennedy AR, Desrosiers A, Terzaghi M, Little JB (1978) Morphometric and histological analysis of the lungs of Syrian golden hamsters. J Anat 125:527–553PubMedCentralPubMedGoogle Scholar
  39. Lamb D, Reid L (1968) Mitotic rates, goblet cell increase and histochemical changes in mucus in rat bronchial epithelium during exposure to sulphur dioxide. J Pathol Bact 96:97–111CrossRefGoogle Scholar
  40. Lane BP, Gordon R (1974) Regeneration of rat tracheal epithelium after mechanical injury. I. The relationship between mitotic activity and cellular differentiation. Proc Soc Exp Biol Med 145:1139–1144CrossRefPubMedGoogle Scholar
  41. Luna LG (1968) Manual of histologic staining methods of the Armed Forces Institute of Pathology. McGraw-Hill, New YorkGoogle Scholar
  42. Marin ML, Gordon RE, Lane BP (1979) Development of tight junctions in rat tracheal epithelium during the early hours after mechanical injury. Am Rev Resp Dis 119:101–106PubMedGoogle Scholar
  43. McDowell EM, Barrett LA, Glavin F, Harris CC, Trump BF (1978) The respiratory epithelium. I. Human bronchus. J Natl Cancer Inst 53:539–549Google Scholar
  44. McDowell EM, Becci PJ, Schürch W, Trump BF (1979) The respiratory epithelium. VII. Epidermoid metaplasia of hamster tracheal epithelium during regeneration following mechanical injury. J Natl Cancer Inst 62:995–1008PubMedGoogle Scholar
  45. McDowell EM, Combs JW, Newkirk C (1982a) A quantitative light and electron microscopic study of hamster tracheal epithelium with special attention to so-called “intermediate cells.” Exp Lung Res (in press)Google Scholar
  46. McDowell EM, Combs JW, Newkirk C (1982b) Acute changes in secretory cells of lower tracheal epithelium of hamsters in response to sub-lethal injury: A quantitative study. Exp Lung Res (in press)Google Scholar
  47. Mohr U, Ketkar MB (1980) Animal model. Spontaneous carcinoma of the lung in hamsters. Am J Pathol 99:521–524PubMedCentralPubMedGoogle Scholar
  48. Montesano R, Saffiotti U, Shubik P (1970) The role of topical and systemic factors in experimental respiratory carcinogenesis. In: Hanna MG, Nettesheim P, Gilbert JR (eds) Inhalation carcinogenesis. AEC Symposium Series 18:353–371Google Scholar
  49. Nettesheim P (1972) Respiratory carcinogenesis with the Syrian golden hamster: A review. Prog Exp Tumor Res 16:185–200CrossRefPubMedGoogle Scholar
  50. Port CD, Baxter DW, Harris CC (1974) Surface morphology of tracheal epithelium in vitamin A deficiency and reversal. In: Karbe E, Park JF (eds) Experimental lung cancer, carcinogenesis and bioassays. Springer, Berlin Heidelberg New York, pp 256–264Google Scholar
  51. Ruddell CL (1967) Epoxy media for 1–2 micron sectioning. Stain Tech 42:253–255Google Scholar
  52. Scarpelli DG, Rao S, Subbarao V, Beversluis M (1981) Regeneration of Syrian golden hamster pancreas and covalent binding of N-nitroso-2,6[3H]dimethylmorpholine. Cancer Res 41:1051–1057PubMedGoogle Scholar
  53. Simpson GEC, Finckh ES (1963) The pattern of regeneration of rat liver after repeated partial hepatectomies. J Pathol Bacteriol 86:361–370CrossRefPubMedGoogle Scholar
  54. Sorokin SP, Hoyt RF (1978) PAS-lead hematoxylin as a stain for smallgranule endocrine cell populations in the lungs, other pharyngeal derivatives and the gut. Anat Rec 192:245–259CrossRefPubMedGoogle Scholar
  55. Spicer SS, Chakrin LW, Wardell JR (1974) Effect of chronic sulfur dioxide inhalation on the carbohydrate histochemistry and histology of the canine respiratory tract. Am Rev Resp Dis 110:13–24PubMedGoogle Scholar
  56. Stockinger L (1964) Beiträge zur Entwicklung und Ultrastruktur des Flimmersaumes. Verh Anat Ges 59:43–52PubMedGoogle Scholar
  57. Townsend SF (1961) Regeneration of gastric mucosa in rats. Am J Anat 109:133–141CrossRefPubMedGoogle Scholar
  58. Wells AB (1970) The kinetics of cell proliferation in the tracheobronchial epithelia of rats with and without chronic respiratory disease. Cell Tissue Kinet 3:185–206PubMedGoogle Scholar
  59. Wilhelm DL (1953) Regeneration of tracheal epithelium. J Pathol Bact 65:543–550CrossRefGoogle Scholar
  60. Wong YC, Buck RC (1971) An electron microscopic study of metaplasia of the rat tracheal epithelium in vitamin A deficiency. Lab Invest 24:55–66PubMedGoogle Scholar

Copyright information

© Springer-Verlag 1982

Authors and Affiliations

  • Kevin P. Keenan
    • 1
  • John W. Combs
    • 2
  • Elizabeth M. McDowell
    • 2
  1. 1.Divison of PathologyWalter Reed Army Institute of ResearchWashington, DCUSA
  2. 2.Department of PathologyUniversity of Maryland School of MedicineBaltimore

Personalised recommendations