Idiopathic interstitial pneumonias: Primum movens: epithelial, endothelial or whatever

Abstract

The pathogenesis of idiopathic interstitial pneumonias (IIPs), particularly of idiopathic pulmonary fibrosis (IPF), is still unknown and the precise nature of the primum movens is strongly debated. Epithelial cells can be the first target of various environmental toxic agents. Both types of pneumocytes may be injured. Type I pneumocyte loss, however, is most conspicuous in fibroblastic foci, the principal sites where irreversible fibrogenesis starts. Epithelial regeneration is highly disturbed: cuboidal and bronchial cells are mainly involved in alveolar repair. These cells, unable to accomplish important functions of normal pneumocytes, secrete various factors inducing migration and proliferation of fibroblasts responsible for progressive extracellular matrix accumulation and lung remodelling. Endothelial cells may also be considered the major players in the initiation of fibrogenic events. Microvascular injury has been largely demonstrated as an early event in IPF lungs. Thrombin as well as other coagulation products has many biological effects such as the activation of different profibrotic factors, which in addition to other fibrogenetic molecules released by stimulated endothelium, are responsible for migration and proliferation of fibroblasts. The old pathogenesis of IPF: chronic inflammation can now be considered the principal event in other non IPF-IIPs. Among inflammatory cells, different cell types have been extensively suggested to play a key role in the pathogenesis of pulmonary fibrosis: granulocytes and eosinophils or mast cells. More recently novel mechanisms underlying the pathogenesis of pulmonary fibrosis have been proposed: bone marrow-derived stem cells may play a crucial role in the fibroproliferative response as well as in epithelial regeneration.