Am. J. Respir. Cell Mol. Biol., Volume 18, Number 6, June, 1998 794-799

Expression of the Bcl-2 Protein in Nasal Epithelia of F344/N Rats during Mucous Cell Metaplasia and Remodeling

Johannes Tesfaigzi, Jon A. Hotchkiss, and Jack R. Harkema

Lovelace Respiratory Research Institute, Albuquerque, New Mexico; and Department of Pathology, College of Veterinary Medicine, Michigan State University, East Lansing, Michigan

Exposure to ozone induces mucous cell metaplasia in rat airway epithelia. During the regeneration process, apoptotic mechanisms may be responsible for eliminating metaplastic cells. Therefore, the present study investigated expression of Bcl-2, a regulator of apoptosis, in ozone-induced mucous cell metaplasias. Adjacent metaplastic mucous cells in nasal airway epithelia that were exposed to ozone were heterogeneous in their expression of Bcl-2; some cells expressed high levels, whereas others expressed low levels or no Bcl-2. On Western blot analysis, Bcl-2 was detected in protein extracts from nasal epithelia of rats exposed to 0.5 ppm ozone for 1 mo but not in control rats exposed to filtered air. The number of metaplastic mucous cells in transitional epithelia of rat nasal airways was increased from 0 to about 200 after 3 and 6 mo of exposure to ozone; only 0 to 10 metaplastic mucous cells remained after a recovery period of 13 wk in rats exposed to ozone for 3 mo. The number of mucous cells of the respiratory epithelium lining the midseptum did not change after ozone exposure or recovery. The percentage of Bcl-2-positive cells lining the midseptum increased from 7 to 14% after a 3- and 6-mo ozone exposure, respectively. In transitional epithelia of the lateral wall and the nasoturbinates and maxilloturbinates, 35 to 55% of cells were Bcl-2-positive after a 1-mo exposure and 10 to 18% after both a 3- and a 6-mo exposure to ozone. Bcl-2 reactivity decreased to 0 to 8% after a recovery period of 13 wk. These observations suggest that Bcl-2 plays a role in the development and resolution of mucous cell metaplasias. This model may be useful in uncovering the role of Bcl-2 during the development and maintenance of metaplastic mucous cells. Disregulation of Bcl-2 expression may be responsible for the sustained mucous cell metaplasia in asthmatics or may allow cells to accumulate and become more susceptible to transformation leading to neoplasia.

This article has been cited by other articles:

				L. Nencioni, G. De Chiara, R. Sgarbanti, D. Amatore, K. Aquilano, M. E. Marcocci, A. Serafino, M. Torcia, F. Cozzolino, M. R. Ciriolo, et al. Bcl-2 Expression and p38MAPK Activity in Cells Infected with Influenza A Virus: IMPACT ON VIRALLY INDUCED APOPTOSIS AND VIRAL REPLICATION J. Biol. Chem., June 5, 2009; 284(23): 16004 - 16015. [Abstract] [Full Text] [PDF]

				B. A. Stout, K. Melendez, J. Seagrave, M. J. Holtzman, B. Wilson, J. Xiang, and Y. Tesfaigzi STAT1 Activation Causes Translocation of Bax to the Endoplasmic Reticulum during the Resolution of Airway Mucous Cell Hyperplasia by IFN-{gamma} J. Immunol., June 15, 2007; 178(12): 8107 - 8116. [Abstract] [Full Text] [PDF]

				L. R. Bartner, N. E. Robinson, M. Kiupel, and Y. Tesfaigzi Persistent mucus accumulation: a consequence of delayed bronchial mucous cell apoptosis in RAO-affected horses? Am J Physiol Lung Cell Mol Physiol, October 1, 2006; 291(4): L602 - L609. [Abstract] [Full Text] [PDF]

				Y. Tesfaigzi Roles of Apoptosis in Airway Epithelia Am. J. Respir. Cell Mol. Biol., May 1, 2006; 34(5): 537 - 547. [Abstract] [Full Text] [PDF]

				J. F. Harris, M. J. Fischer, J. R. Hotchkiss, B. P. Monia, S. H. Randell, J. R. Harkema, and Y. Tesfaigzi Bcl-2 Sustains Increased Mucous and Epithelial Cell Numbers in Metaplastic Airway Epithelium Am. J. Respir. Crit. Care Med., April 1, 2005; 171(7): 764 - 772. [Abstract] [Full Text] [PDF]

				Y. Tesfaigzi, J. F. Harris, J. A. Hotchkiss, and J. R. Harkema DNA synthesis and Bcl-2 expression during development of mucous cell metaplasia in airway epithelium of rats exposed to LPS Am J Physiol Lung Cell Mol Physiol, February 1, 2004; 286(2): L268 - L274. [Abstract] [Full Text] [PDF]

				J. E. Foster, K. Gott, M. R. Schuyler, W. Kozak, and Y. Tesfaigzi LPS-induced neutrophilic inflammation and Bcl-2 expression in metaplastic mucous cells Am J Physiol Lung Cell Mol Physiol, August 1, 2003; 285(2): L405 - L414. [Abstract] [Full Text] [PDF]

				Y. Tesfaigzi, M. J. Fischer, M. Daheshia, F. H. Y. Green, G. T. De Sanctis, and J. A. Wilder Bax is Crucial for IFN-{gamma}-Induced Resolution of Allergen- Induced Mucus Cell Metaplasia J. Immunol., November 15, 2002; 169(10): 5919 - 5925. [Abstract] [Full Text] [PDF]

				S.-Z. Wang, C. L. Rosenberger, T. M. Espindola, E. G. Barrett, Y. Tesfaigzi, D. E. Bice, and K. S. Harrod CCSP modulates airway dysfunction and host responses in an Ova-challenged mouse model Am J Physiol Lung Cell Mol Physiol, November 1, 2001; 281(5): L1303 - L1311. [Abstract] [Full Text] [PDF]

				Y. Tesfaigzi, M. J. Fischer, A. J. Martin, and J. Seagrave Bcl-2 in LPS- and allergen-induced hyperplastic mucous cells in airway epithelia of Brown Norway rats Am J Physiol Lung Cell Mol Physiol, December 1, 2000; 279(6): L1210 - L1217. [Abstract] [Full Text] [PDF]

				J. R. Harkema, J. A. Hotchkiss, E. B. Barr, C. B. Bennett, M. Gallup, J. K. Lee, and C. Basbaum Long-Lasting Effects of Chronic Ozone Exposure on Rat Nasal Epithelium Am. J. Respir. Cell Mol. Biol., March 1, 1999; 20(3): 517 - 529. [Abstract] [Full Text]