Fig 2.

Events occurring in vivo after epithelial denudation, leaving an uninjured basement membrane. No bleeding occurs, but the basement membrane is not left naked. Plasma exudation produces and continuously supplies a gel-like cover involving a fibrin-fibronectin net. Also, leukocytes, especially neutrophils, are recruited and activated. Eosinophils already present in the airway are activated by primary cytolysis. The gel serves as a highly active provisional barrier and milieu for speedy epithelial regeneration. All epithelial cell types bordering the denuded patch, notably including both secretory and ciliated cells, promptly dedifferentiate into flattened regeneration cells. As in micrographs of bronchi of asthmatic patients, basal cells might not be readily distinguished from regeneration cells. Loosely linked, the latter migrate from all sides over the denuded patch at a speed of several micrometers per minute. When a new cell cover is complete, plasma exudation stops, the plasma-derived gel dislodges, and proliferation plus redifferentiation toward a normal epithelium begins in the previously denuded area. Epithelial regeneration in vivo alone induces recruitment and activation of granulocytes, hyperexudation, hypersecretion, proliferation not only of epithelial cells but also of fibrocyte/smooth muscle cells, and thickening of the epithelial reticular basement membrane. In patients with desquamating asthma, multiple patches of epithelial regeneration would contribute to known pathogenic inflammatory and remodeling effects. DCC, Dedifferentiating ciliated cell internalizing or shedding its cilia, flattening, and migrating; DRC, dedifferentiated mesenchymal-like regeneration cells migrating speedily; DSC, dedifferentiating secretory cell releasing its secretory granules, flattening, and migrating; E, eosinophils undergoing cytolysis and liberating its protein-rich granules; IEG, venular interendothelial gaps through which nonsieved plasma proteins extravasate; N, neutrophils; PFSM, proliferating fibrocytes/smooth muscle cells; TRBM, thickened reticular basement membrane.