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© 2006 The American Thoracic Society
doi: 10.1513/pats.200605-126SF
Airway Epithelial Repair, Regeneration, and Remodeling after Injury in Chronic Obstructive Pulmonary Disease
Institut National de la Santé et de la Recherche Médicale, INSERM UMR-S 514, and Centre Hospitalier Universitaire Maison Blanche, Reims, France
Correspondence and requests for reprints should be addressed to Edith Puchelle, Ph.D., INSERM UMR-S 514, Centre Hospitalier Universitaire Maison Blanche, 45 rue Cognacq Jay, 51092 Reims Cedex, France. E-mail: edith.puchelle{at}univ-reims.fr
ABSTRACT
In chronic obstructive pulmonary disease (COPD), exacerbations are generally associated with several causes, including pollutants, viruses, bacteria that are responsible for an excess of inflammatory mediators, and proinflammatory cytokines released by activated epithelial and inflammatory cells. The normal response of the airway surface epithelium to injury includes a succession of cellular events, varying from the loss of the surface epithelium integrity to partial shedding of the epithelium or even complete denudation of the basement membrane. The epithelium then has to repair and regenerate to restore its functions, through several mechanisms, including basal cell spreading and migration, followed by proliferation and differentiation of epithelial cells. In COPD, the remodeling of the airway epithelium, such as squamous metaplasia and mucous hyperplasia that occur during injury, may considerably disturb the innate immune functions of the airway epithelium. In vitro and in vivo models of airway epithelial wound repair and regeneration allow the study of the spatiotemporal modulation of cellular and molecular interaction factors—namely, the proinflammatory cytokines, the matrix metalloproteinases and their inhibitors, and the intercellular adhesion molecules. These factors may be markedly altered during exacerbation periods of COPD and their dysregulation may induce remodeling of the airway mucosa and a leakiness of the airway surface epithelium. More knowledge of the mechanisms involved in airway epithelium regeneration may pave the way to cytoprotective and regenerative therapeutics, allowing the reconstitution of a functional, well-differentiated airway epithelium in COPD.
Key Words: airway epithelial differentiation • bacterial injury • inflammation • remodeling • wound repair
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