Extracellular Matrix in Acute Respiratory Distress Syndrome

Acute Respiratory Distress Syndrome (ARDS) is a life-threatening condition characterised by acute onset of hypoxemic respiratory failure, often initiated by extensive lung inflammation. Diffuse alveolar damage (DAD), a histological hallmark of ARDS, can potentially progress to lung fibrosis, which is marked by significant lung interstitial structural alterations. Extracellular matrix (ECM), the dynamic framework which provides structural support to tissues, undergoes remodelling during ARDS. However, detailed and comprehensive knowledge of the occurrence of remodelling and which specific ECM components are involved during ARDS progression, remains limited. Therefore, this thesis aimed to investigate the characteristics of ECM remodelling in systemic inflammation and ARDS, and explored the impact of an altered ECM environment on inflammation. We detected increased circulating biomarkers of ECM synthesis and degradation in systemic inflammation, alongside changes in ECM composition in lung tissue of ARDS patients. To further assess the impact of an altered ECM on immune responses, we constructed an in vitro neutrophil-ECM model using ECM generated by human lung fibroblasts. ECM generated in presence of pro-inflammatory, but not pro-fibrotic, stimulus tended to increase neutrophil viability. These results suggested altered ECM environments could induce differential neutrophil responses, therefore creating different immune consequences. This work uncovers a bidirectional relationship where inflammation triggers ECM remodelling, and remodelled ECM impacts inflammatory events, paving the road to further explore the possible roles of ECM and remodelling processes in ARDS.