TY - JOUR T1 - Epithelial apoptosis in the initiation of lung fibrosis JF - European Respiratory Journal JO - Eur Respir J SP - 7s LP - 9s DO - 10.1183/09031936.03.00000303 VL - 22 IS - 44 suppl AU - B.D. Uhal Y1 - 2003/09/20 UR - http://erj.ersjournals.com/content/22/44_suppl/7s.abstract N2 - This work was supported by PHS HL‐45136, by the American Heart Association and by the MSU Foundation. Apoptosis in the lung is a relatively new area of research that is receiving increasing attention. A growing body of evidence indicates that apoptosis is controlled in a tissue- and cell type-specific manner; for this reason, the regulation of apoptosis in specific cell types of the lung is currently an area of intensive research 1. This article provides evidence supporting the viewpoint that apoptosis of alveolar epithelial cells is a key event in the initiation of fibrotic lesions, and will discuss a working hypothesis to explain possible mechanisms by which epithelial apoptosis can lead to lung fibrogenesis. Recent evidence implicates important roles for apoptosis in animal models of lung injury/repair or remodelling and in lung biopsies from patients with a variety of lung disorders. For example, apoptosis plays a critical role in postnatal lung development 2 and in the normal resolution of lung inflammation by the regulated removal of unneeded cells such as granulocytes, without the release of damaging histotoxins 3. Dexamethasone has been known for many years to induce apoptosis in some leukocyte subsets, and apoptosis is an important mechanism underlying the anti-inflammatory action of this and other glucocorticoids 4. Considerable literature now supports a role for apoptosis in the remodelling of lung tissue after acute lung injury, both for the clearance of excess epithelial stem cells after hyperplastic repair 5 and for the normal removal of excess mesenchymal cells from resolving lesions 6. Extensive apoptosis is found in the lungs of patients with idiopathic pulmonary fibrosis (IPF) 7, 8 and in animals of this disease 9, 10. Recent evidence also suggests a role for apoptosis in the tissue remodelling … ER -