Increased levels of glycosaminoglycans in lungs from patients with IPF

Rationale: Idiopathic pulmonary fibrosis (IPF) is characterized by loss of lung function due to aberrant deposition of extracellular matrix (ECM) constituents. One such constituent is glycosaminoglycans (GAGs) consisting of unbranched polymers of repeating disaccharides. They are highly negatively charged which renders them the ability to interact with important mediators in the IPF pathogenesis. The abundance and localisation of GAGs in relation to tissue density is not known in IPF. The aim of this study was therefore to measure GAGs in lung samples from IPF patients and from control subjects. Methods: Lung tissue samples were collected from more or less dense areas in distal lungs from IPF patients (n=8) and from donor lungs (n=4). GAGs were isolated and quantified by HPLC after fluorochrome labelling. The total collagen content was quantified by the amount of hydroxyproline and fibrillar collagen was measured by picro-sirius red staining. Results: The total amount of heparan sulfate (HS), chondroitin/dermatan sulfate (CS/DS) and hyaluronan (HA) was significantly higher in denser areas of IPF lungs compared to less dense areas (p ≤ 0.01 for HS, p ≤ 0.05 for CS/DS and p ≤ 0.01 for HA) and also compared to control lungs. HA was significantly increased in less fibrotic areas compared to control lungs. Moreover, the amount of GAGs in IPF tissue correlated with the volume fraction of picro-sirius red stain but not with the hydroxyproline content. Conclusions: Our results show that GAGs are quantatively elevated in fibrotic lesions characterized by high tissue density and increased levels of fibrillar collagen in IPF. This may create an altered ECM niche that promotes an active remodelling process.