Figure 1.

The normal lung epithelium composition changes along the respiratory tree from proximal airways to alveolar areas. Secretory cells produce the mucus lining the airways, which is moved upstream by the ciliated beats originating from ciliated cells. Basal cells have a local progenitor function, possessing the ability to differentiate into several cell types, including secretory and ciliated cells. In small airways, basal and secretory cells are progressively replaced by club (ex-Clara) cells, which can serve as local facultative progenitors (besides basal cells), secrete components of the bronchiolar lining fluid, and play a detoxifying role through their expression of cytochrome p450. In the alveoli, alveolar type-1 epithelial cells (AEC1) are responsible for gas exchange, while alveolar type-2 epithelial cells (AEC2) produce surfactant and serve as local progenitors. Epithelial cells are connected by tight- and adherens junctions, forming a continuous layer separating the intra-luminal content from the submucosal environment and regulating intercellular permeability. Tight junctions are composed of integral membrane proteins like claudins and occludins, which are linked to the cytoskeleton through cytosolic protein complexes such as Zonula Occludens (ZO). Adherens junctions, formed by E-cadherin proteins, linked to the cytoskeletion by catenins are responsible for the maintenance of cell-cell adhesion while being involved in many intracellular signaling and transcriptional pathways. MCC, mucociliary clearance.