Fibroblasts as matrix modulating cells in asthma and COPD

Sammanfattning: Chronic lung diseases such as asthma and chronic obstructive pulmonary disease (COPD) are two lung diseases that are continuously increasing worldwide. Despite extensively research to find curative treatment, no so such therapy exists today. New hypothesis suggests that an aberrant chronic wound healing process takes place which involves both the classical inflammation and more chronic changes of the structural environment where the mesenchymal cell phenotypes such as the fibroblasts play a key role. This phenomenon is defined as airway remodeling and is characterized by a deposition of extracellular matrix (ECM) molecules such as collagens and proteoglycans. Importantly, hitherto available studies have only studied fibroblast from central airways from humans where the role of the fibroblast might be different compared to the distal lung. The aim of the present thesis was to study the different fibroblast phenotypes and their biological role from central and distal localizations from human lung in controls, rhinitis, asthmatics and CODP subjects. Another aim was to investigate the possible origin (circulating progenitor cells) of these cells and thereby highlight the heterogeneity of fibroblast phenotypes resident within the human lung. This investigation demonstrated the novel finding that different fibroblast phenotypes are present in human adult lung. Moreover, they are different in asthma and COPD which suggest disease related fibroblasts that could be of fundamental importance in lung disease.