DNA synthesis and Bcl-2 expression during development of mucous cell metaplasia in airway epithelium of rats exposed to LPS

Abstract

Tesfaigzi, Yohannes, J. Foster Harris, Jon A. Hotchkiss, and Jack 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 286: L268-L274, 2004. First published October 3, 2003 10.1152/ ajplung.00172.2003.-Exposure of pulmonary airways to environmental toxins and allergens may cause proliferation of airway epithelial cells and mucous cell metaplasia (MCM); however, it is unclear to what extent proliferating cells differentiate into mucus-storing cells and contribute to MCM. Our previous studies demonstrated that Bcl-2, an inhibitor of apoptosis with cell cycle regulatory functions, is expressed in metaplastic mucous cells. The purpose of the present study was to investigate the number of metaplastic mucous cells that are derived from proliferating epithelial cells and whether Bcl-2 has a role in cell cycle entry in these cells. Rats were intratracheally instilled with 100 g of LPS from Pseudomonas aeruginosa in 500 l of saline, and proliferating airway cells were labeled with bromodeoxyuridine (BrdU) by implanting a subcutaneous osmotic pump 24 h before instillation. The volume of stored mucosubstance and the number of mucous cells were increased 10-and 3-fold, respectively, from 24-48 h after instillation. The number of total epithelial cells per millimeter of basal lamina increased, and the number of serous cells per millimeter of basal lamina decreased during this time. Approximately 50% of Alcian blue-periodic acid Schiff-stained mucous cells were labeled with BrdU at 48 h after instillation, suggesting that one-half of the secretory cells were derived from proliferating cells. Furthermore, 50% of the Bcl-2-positive mucous cells were BrdU negative and therefore derived from nonproliferating, preexisting cells. Our findings demonstrate that preexisting and proliferating cells differentiate into mucous cells and compose LPS-induced metaplasia and that Bcl-2 does not have cell cycle regulatory function in these cells.bromodeoxyuridine; secretory cell; apoptosis; electron microscopy EXPOSURE OF THE PULMONARY airways to inhaled toxins or allergens may cause injury to the airway epithelium that results in an acute inflammatory response, proliferation of surviving epithelial cells, and mucous cell metaplasia (MCM). MCM occurs in respiratory epithelia when nonproliferating, preexisting or proliferating epithelial cells differentiate into mucous cells in areas where no or few mucous cells are normally present. Increased numbers of airway mucous cells is a prominent feature of a number of bronchial diseases in humans, including chronic bronchitis (13), asthma (24), and cystic fibrosis (28). Proliferation of epithelial cells was reported in airways of subjects with chronic bronchitis (4); however, it is unknown to what extent existing or proliferating cells differentiate into mucus-storing cells and contribute to the development of MCM. Exposure to LPS (endotoxin) from the outer membrane of gram-negative ...

STAT1 Activation Causes Translocation of Bax to the Endoplasmic Reticulum during the Resolution of Airway Mucous Cell Hyperplasia by IFN-γ

“…In wild-type mice exposed to allergen for 15 days, ER Bax was detected in mucous cells, suggesting that during resolution hyperplastic mucous cells are targeted for removal. Several studies have shown that following injury to the airway epithelium, a large proportion of the hyperplastic and cycling cells are secretory cells (49 -51) and mucous cells arise mainly by self-replication and differentiation of pre-existing cells (52,53). Because mucous cells are the hyperplastic cells, they may be by default susceptible to cell death and elimination in vivo during resolution.…”

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Cigarette Smoke Suppresses Bik To Cause Epithelial Cell Hyperplasia and Mucous Cell Metaplasia

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