Puchelle Edith, Zahm Jean-Marie, Tournier Jean-Marie, Coraux Christelle
INSERM UMR-S 514, Centre Hospitalier Universitaire Maison Blanche, 45 rue Cognacq Jay, 51092 Reims Cedex, France.
Proc Am Thorac Soc. 2006 Nov;3(8):726-33. doi: 10.1513/pats.200605-126SF.
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.
在慢性阻塞性肺疾病（COPD）中，病情加重通常与多种原因相关，包括污染物、病毒、可导致炎性介质过量产生的细菌，以及活化的上皮细胞和炎性细胞释放的促炎细胞因子。气道表面上皮对损伤的正常反应包括一系列细胞事件，从表面上皮完整性丧失到上皮部分脱落，甚至基底膜完全剥脱。然后，上皮细胞必须通过多种机制进行修复和再生以恢复其功能，这些机制包括基底细胞的伸展和迁移，随后是上皮细胞的增殖和分化。在COPD中，气道上皮重塑，如损伤期间发生的鳞状化生和黏液增生，可能会严重干扰气道上皮的固有免疫功能。气道上皮伤口修复和再生的体外和体内模型有助于研究细胞和分子相互作用因子的时空调节，即促炎细胞因子、基质金属蛋白酶及其抑制剂以及细胞间黏附分子。在COPD病情加重期间，这些因子可能会发生显著改变，其失调可能会导致气道黏膜重塑和气道表面上皮通透性增加。对气道上皮再生所涉及机制的更多了解可能为细胞保护和再生治疗铺平道路，从而在COPD中重建功能正常、分化良好的气道上皮。
