Pathogenic mechanisms in the development of diffuse pulmonary fibrosis

ABSTRACT

Diffuse pulmonary fibrosis is characterized by abnormal proliferation of mesenchymal cells, specifically fibroblasts and myofibroblasts, and by the accumulation of excessive amounts of matrix proteins, mainly collagens. The development of this pathological process is preceded by an inflammatory response, often dominated by macrophages and lymphocytes, which is mediated by the local release of chemoattractant factors, acting coordinately with an upregulation of cell-surface adhesion molecules. A subsequent persisting fibroproliferative reaction, in both interstitial and intraalveolar spaces, with progressive collagen accumulation distorts the lung architecture irreversibly. Excessive collagen deposition is the result of an imbalance in the collagen turnover rates characterized by a transient increase in collagen synthesis and a decrease in collagen degradation. Fibrosis is considered otherwise to be the final common pathway of a variety of lung disorders, and in this context, the diagnosis of pulmonary fibrosis implies the recognition of an advanced stage in the evolution of a complex process of abnormal repair.