DNA synthesis and Bcl-2 expression during development of mucous cell metaplasia in airway epithelium of rats exposed to LPS.
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 microg of LPS from Pseudomonas aeruginosa in 500 microl 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.
Tesfaigzi
Yohannes
Y
Lovelace Respiratory Research Institute, 2425 Ridgecrest Dr., SE, Albuquerque, NM 87108, USA. ytesfaig@lrri.org
Harris
J Foster
JF
Hotchkiss
Jon A
JA
Harkema
Jack R
JR
D000818:Animals; D002452:Cell Count; D002455:Cell Division; D004247:DNA / Q000096:biosynthesis; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008679:Metaplasia; D008854:Microscopy, Electron; D009092:Mucous Membrane / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D011014:Pneumonia / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D020545:Respiratory Mucosa / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology
D008070:Lipopolysaccharides; D019253:Proto-Oncogene Proteins c-bcl-2; D004247:DNA