Summary
In companion papers we described in detail the morphologic changes that occur during tracheal regeneration following focal mechanical injury (Keenan et al. 1982a), and the proliferative events that occur following multifocal injury, particularly the dominant role played by the secretory cell population in the regenerative process. In this paper the histogenesis of epidermoid metaplasia and restoration of normal mucociliary epithelium following mechanical injury was studied in hamster tracheal epithelium with single pulse or continuous infusion of tritiated thymidine (3HTdR) combined with colchicine blockade of metaphase mitoses. Both small and large wounds were produced in the same animal, in the dorsal and ventral tracheal semicircles respectively. At 12 h following injury, 14.2% of the dorsal epithelial cells and 34.6% of the ventral epithelial cells were lost. Viable cells migrated into the denuded wound sites, covering the small wounds by 12 h and the larger wounds by 48 h. By 27 h a peak mitotic rate (MR) was reached in the dorsal epithelium (MR = 18.1%), but mitotic activity in the ventral epithelium did not peak until 33 h (MR = 13.3%). In both tracheal semicircles, secretory cells accounted for over 76% of the labeled mitotic cells. Ciliated cells did not label or divide. Epidermoid metaplasia was first observed at 33 h in both semicircles. It was transient in the small wounds, but persisted through 168 h in the large wounds. Almost all the epidermoid cells were labeled by continuous3HTdR infusion. A very few pre-ciliated cells appeared first at 33 h but they peaked in numbers at 72 h in both the dorsal (8.0%) and ventral (5.5%) semicircles. These large, pale staining cells were not labeled by single pulse3HTdR but were labeled by continuous3HTdR infusion. Later, large, pale staining cells morphologically similar to pre-ciliated cells, and with identical labeling patterns, were observed budding cilia. Ciliated cell numbers were restored to control level in the dorsal semicircle by 168 h, but only to 84% of control values in the ventral semicircle, where epidermoid metaplasia persisted. These data suggest that secretory cells have a greater proliferative potential than basal cells in regenerating tracheal epithelium, and that they contribute to the development of both transient and persistent epidermoid metaplasia and the production of new secretory cells. Moreover, these proliferating secretory cells produce ciliated cells via a transient pre-ciliated cell which develops cilia and matures in the regenerating epithelium.
Similar content being viewed by others
References
Asmundsson T, Kilburn KH, McKenzie WN (1973) Injury and metaplasia of airway cells due to SO2. Lab Invest 29:41–53
Auerbach O, Stout AP, Hammond EC, Garfinkel L (1961) Changes in bronchial epithelium in relation to cigarette smoking and in relation to lung cancer. New Eng J Med 265:253–267
Auerbach O, Hammond EC, Garfinkel L (1979) Changes in bronchial epithelium in relation to cigarette smoking, 1955–1960 vs.1970–1977. New Eng J Med 300:381–386
Becci PJ, McDowell EM, Trump BF (1978a) The respiratory epithelium. IV. Histogenesis of epidermoid metaplasia and carcinoma in situ in the hamster. J Natl Cancer Inst 61:577–586
Becci PJ, McDowell EM, Trump BF (1978b) The respiratory epithelium. VI. Histogenesis of lung tumors induced by benzo(a) pyrene-ferric oxide in the hamster. J Natl Cancer Inst 61:607–618
Bils RF, Christie BR (1980) The experimental pathology of oxidant and air pollutant inhalation. Internatl Review Exp Pathol 21:195–293
Bindreiter M, Schupper J, Stockinger L (1968) Zellproliferation und Differenzierung im Trachealepithel der Ratte. Exp Cell Res 50:377–382
Black H, Ackerman LV (1952) The importance of epidermoid carcinomain situ in the histogenesis of carcinoma of the lung. Ann Surg 136:44–54
Boatman ES, Sato S, Frank R (1974) Acute effects of ozone on cat lungs. Am Rev Resp Dis 110:157–169
Bolduc R, Reid L (1976) Mitotic index of the bronchial and alveolar lining of the normal rat lung. Am Rev Resp Dis 114:1121–1128
Boren HG, Paradise LJ (1978) Cytokinetics of lung. In: Harris CC (ed) Pathogenesis and therapy of lung cancer. Marcel Dekker, New York, pp 369–418
Breeze RG, Wheeldon EB (1977) The cells of the pulmonary airways. Am Rev Resp Dis 116:705–777
Carter D, Eggleston JC (1980) Tumors of the lower respiratory tract. Atlas of tumor pathology, second series, fascicle 17. Armed Forces Institute of Pathology, Washington, D.C.
Chakrin LW, Saunders LZ (1974) Experimental chronic bronchitis. Pathology in the dog. Lab Invest 30:145–154
Cireli E (1966) Elektronenmikroskopische Analyse der prä- und postnatalen Differenzierung des Epithels der oberen Luftwege der Ratte. Z Mikrosk Anat Forsch 74:132–178
Clyde WA (1980) Experimental models for study of common respiratory viruses. Envir Health Persp 35:107–112
Collier AM (1980) Injury of respiratory epithelium. Envir Health Persp 35:83–88
Dahlgren SE, Dalen H, Dalhamn T (1972) Ultrastructural observations on chemically induced inflammation in guinea pig trachea. Virchows Arch [Zell Pathol] 11:211–223
Elmes PC, Bell D (1963) The effects of chlorine gas on the lungs of rats with spontaneous pulmonary disease. J Pathol 86:317–326
Emura M, Mohr U (1975) Morphological studies on the development of tracheal epithelium in the Syrian golden hamster. I. Light microscopy. Z Versuchstierk Bd 17:14–26
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 35:246–257
Fleischmann W, Russel O, Fleischmann S (1962) LD 50 and minimal effective anti-mitotic dose of colchicine in various rodents. Med Exp 6:101–104
Florey J, Carleton HM, Wells AQ (1932) Mucus secretion in the trachea. Br J Exp Pathol 13:269–284
Frasca JM, Auerbach O, Parks VR, Jamieson JD (1968) Electron microscopic observations on the bronchial epithelium of dogs. II. Smoking dogs. Exp Mol Pathol 9:380–399
Freeman G, Haydon GB (1964) Emphysema after low-level exposure to NO2. Arch Envir Health 8:125–128
Gabridge MG, Agee CC, Cameron AM (1977) Differential distribution of ciliated epithelial cells in the trachea of hamsters: implications for studies of pathogenesis. J Inf Dis 135:9–19
Gordon RE, Lane BP (1980) Fate of regenerative tracheal epithelial cells in response to mild injury. J Cell Biol 87:15a
Harris CC, Sporn MG, Kaufman DG, Smith JM, Baker MS, Saffiotti U (1971) Acute ultrastructural effects of benzo(a) pyrene and ferric oxide on the hamster tracheobronchial epithelium. Cancer Res 31:1977–1989
Harris CC, Sporn MB, Kaufman DG, Smith JM, Jackson FE, Saffiotti U (1972) Histogenesis of squamous metaplasia in the hamster tracheal epithelium caused by vitamin A deficiency or benzo(a)pyrene-ferric oxide. J Natl Cancer Inst 48:743–761
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 12:259–269
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 51:1059–1062
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 67:158a
Holtzer H, Rubinstein N, Fellini S, Yeoh G, Chi J, Birnbaum J, Okayama M (1975) Lineages, quantal cell cycles, and the generation of cell diversity. Quart Rev Biophys 8:523–557
Kalnins VI, Porter KR (1969) Centriole replication during ciliogenesis in the chick tracheal epithelium. Z Zellforsch Mikrosk Anat 100:1–30
Keenan KP, Combs JW, McDowell EM (1982a) Regeneration of hamster tracheal epithelium after mechanical injury. I. Quantitative study of cellular proliferation and phenotypic modulation in response to a focal lesion. Virchow Arch [Cell Pathol] 41:193–214
Keenan KP, Combs JW, McDowell EM (1982b) Regeneration of hamster tracheal epithelium after mechanical injury. II. Stathmokinetic and autoradiographic studies of the effects of multifocal injury on epithelial proliferation. Virchows Arch [Cell Pathol] 41:231–252
Keenan KP, Wilson TS, McDowell EM (1982c) Regeneration of hamster tracheal epithelium after mechanical injury. IV. Histochemical immunocytochemical and ultrastructural studies. Submitted to Virchows Arch [Cell Pathol]
Klein-Szanto AJP, Topping DC, Heckman CA, Nettesheim P (1980 a) Ultrastructural characteristics of carcinogen-induced nondysplastic changes in tracheal epithelium. Am J Pathol 98:61–82
Klein-Szanto AJP, Topping DC, Heckman CA, Nettesheim P (1980b) Ultrastructural characteristics of carcinogen-induced dysplastic changes in tracheal epithelium. Am J Pathol 98:83–100
Kuhn G (1976) The cells of the lung and their organelles. In: Crystal RG (ed) The biochemical basis of pulmonary function. Marcel Dekker, New York, pp 3–48
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 96:97–111
Lamb D, Reid L (1969) Goblet cell increase in rat bronchial epithelium after exposure to cigarette and cigar tobacco smoke. Br Med J 1:33–35
Matulionis DH (1975) Light and electron microscopic study of the effect of ZnSO4 on mouse nasal respiratory epithelium and subsequent responses. Anat Rec 183:63–82
McDowell EM, McLaughlin JS, Merenyi DK, Kieffer RF, Harris CC, Trump BF (1978) The respiratory epithelium. V. Histogenesis of lung carcinomas in the human. J Natl Cancer Inst 61:587–606
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 62:995–1008
McDowell EM, Combs JW, Newkirk C (1982) A quantitative light and electron microscopic study of hamster tracheal epithelium with special attention to so-called “intermediate cells.” Exp Lung Res (in press)
Miller WS (1932) The epithelium of the lower respiratory tract. In: Cowdry EV (ed) Special Cytology 2nd ed. Hoeber, New York, pp 133–150
Mossman BT, Kessler JB, Ley BW, Craighead JE (1977) Interaction of crocidolite asbestos with hamster respiratory mucosa in organ culture. Lab Invest 36:131–139
Mueller GC, Kajiwara K, Kim UH, Graham J (1978) Proposed coupling of chromatin replication, hormone action, and cell differentiation. Cancer Res 38:4041–4045
Muse KE, Collier AM, Baseman JB (1977) Scanning electron microscopic study of hamster tracheal organ cultures infected withBordetella pertussis. J Infect Dis 136:768–777
Nasiell M (1963) The general appearance of the bronchial epithelium in bronchial carcinoma: A histopathologic study with some cytological viewpoints. Acta Cytol 7:97–106
Nettesheim P (1971) Induction of squamous cell tumors in the respiratory tract of mice. Proc Am Assoc Cancer Res 12:29
Nettesheim P (1972) Respiratory carcinogenesis with the Syrian golden hamster: A review. Prog Exp Tumor Res 16:185–200
Nettesheim P, Klein-Szanto JP, Marchok AC, Steele VE, Terzaghi M, Topping DC (1981) Studies of neoplastic development in respiratory tract epithelium. Arch Pathol Lab Med 105:1–10
Pierce GB (1974) Neoplasms, differentiations and mutations. Am J Pathol 77:103–118
Pierce GB, Cox WF (1978) Neoplasms as caricatures of tissue renewal. In: Saunders GF (ed) Cell differentiation and neoplasia. Raven Press, New York, pp 57–66
Port CD, Henry MC, Kaufman DG, Harris CC, Ketels KV (1973) Acute changes in the surface morphology of hamster tracheobronchial epithelium following benzo(a)pyrene and ferric oxide administration. Cancer Res 33:2498–2506
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 257–264
Reid L (1963) An experimental study of hypersecretion of mucus in the bronchial tree. Br J Exp Pathol 44:437–445
Reznik-Schüller H, Mohr U (1974a) Investigations on the carcinogenic burden by air pollution in man. IX. Early pathological alterations of the bronchial epithelium in Syrian golden hamsters after intratracheal instillation of benzo(a)pyrene. I. Morphological studies from semithin sections. Zentralbl Bakteriol [B] 159:493–502
Reznik-Schüller H, Mohr U (1974b) Investigations on the carcinogenic burden by air pollution in man. X. Morphological changes of the tracheal epithelium in Syrian golden hamsters during the first 20 weeks of benzo(a)pyrene instillation: An ultrastructural study. Zentralbl Bakteriol [B] 159:503–525
Reznik-Schüller H, Mohr U (1975) Investigations on the carcinogenic burden by air pollution in man. XII. Early pathological alterations of the bronchial epithelium in Syrian golden hamsters after intratracheal instillation of benzo(a)pyrene. II. Further ultrastructural studies. Zentralbl Bakteriol [B] 160:108–129
Richter-Reichhelm HB, Emura M, Althoff J (1980a) Scanning electron microscopical investigations on the respiratory epithelium of the Syrian golden Hamster. I. Postnatal differentiation. Zentralbl Bakteriol [Naturwiss] 171:424–432
Richter-Reichhelm HB, Emura M, Althoff J (1980b) Scanning electron microscopical investigations on the respiratory epithelium of the Syrian golden hamster. II. In vitro differentiation. Zentralbl Bakteriol [Naturwiss] 171:433–440
Saffiotti U, Cefis F, Kolb L (1968) A method for the experimental induction of bronchogenic carcinoma. Cancer Res 28:104–124
Sanderud K (1958) Squamous metaplasia of the respiratory tract epithelium 5. A contribution to the pathogenesis of metaplasia. Two experimental studies. Acta Pathol Microbiol Scand 44:345–362
Schiff LJ, Byrne MM, Ketels KV, Brown WT, Graham JA (1979) A scanning electron microscope study of developing hamster tracheal epithelium in organ culture. Differentiation 15:49–55
Smolich JJ, Stratford BF, Maloney JE, Ritchie BC (1967) Postnatal development of the epithelium of larynx and trachea in the rat: scanning electron microscopy. J Anat 124:657–673
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 110:13–24
Steinman RM (1968) An electron microscopic study of ciliogenesis in development epidermis and trachea in the embryo ofXenopus laevis. Am J Anat 122. 19–56
Stenbäck F (1973) Morphologic characteristics of experimentally induced lung tumors and their precursors in hamsters. Acta Cytol 17:476–486
Stockinger L (1964) Beiträge zur Entwicklung und Ultrastruktur des Flimmersaumes. Verh Anat Ges 59:43–52
Stockinger L, Cireli E (1965) Eine bisher unbekannte art der zentriolenvermehrung. Z Zellforsch Mikrosk Anat 68:733–740
Trump BF, McDowell EM, Glavin F, Barrett LA, Becci PJ, Schürch W, Kaiser HE, Harris CC (1978) The respiratory epithelium. III. Histogenesis of epidermoid metaplasia and carcinoma in situ in the human. J Natl Cancer Inst 61:563–575
Wilhelm DL (1953) Regeneration of tracheal epithelium. J Pathol 65:543–550
Wolbach SB, Howe PR (1925) Tissue changes following deprivation of fat soluble A vitamin. J Exp Med 42:753–777
Wong YC, Buck RC (1971) An electron microscopic study of metaplasia of the rat tracheal epithelium in vitamin A deficiency. Lab Invest 24:55–66
Author information
Authors and Affiliations
Additional information
The opinions and assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of Defense. The experiments reported herein were conducted according to the principles set forth in the “Guide for the Care and Use of Laboratory Animals,” Institute of Laboratory Animal Resources, National Research Council, DHEW Publ. No. 78-23. This is contribution No. 1271 from the Cellular Pathobiology Laboratory, Department of Pathology, University of Maryland School of Medicine
This work was supported in part by USPHS NIH Grant HL #24722
Submitted by K.P.K. in partial fulfiment of a Doctor of Philosophy degree from the Department of Pathology, University of Maryland School of Medicine
Rights and permissions
About this article
Cite this article
Keenan, K.P., Combs, J.W. & McDowell, E.M. Regeneration of hamster tracheal epithelium after mechanical injury. Virchows Archiv B Cell Pathol 41, 231–252 (1982). https://doi.org/10.1007/BF02890283
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/BF02890283