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Regeneration of hamster tracheal epithelium after mechanical injury

III. Large and small lesions: Comparative stathmokinetic and single pulse and continuous thymidine labeling autoradiographic studies

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Virchows Archiv B Cell Pathology Including Molecular Pathology

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.

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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

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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

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