From granuloma to fibrosis in interstitial lung diseases: molecular and cellular interactions

Granuloma is a feature of many chronic interstitial lung diseases, and may serve as a focus for subsequent fibrosis. Granulomas are composed of structured masses of cells of the macrophage lineage, which adopt an epithelioid aspect, interspersed with lymphocytes. They are formed around local centres of irritation. During their resolution, fibroblasts congregate around the structures and may penetrate the interior. In many cases, granulomas can disappear without leaving lasting traces. However, especially when damage has occurred to the surrounding tissue, permanent scarring and fibrosis may occur. Both types of cell present in the granuloma are capable of secreting a number of factors influencing the accumulation and proliferation of fibroblasts, both positively and negatively. The possible roles played by the different factors and, especially, interactions between them are discussed in the light of fibrosis formation. Possible therapeutic interventions are summarized.