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Thesis defense Sofia Morsing

2O21: A Vascular Odyssey

On 3 December 2021 (16:00) Sofia Morsing defended her thesis '2O21: A Vascular Odyssey' at the University of Amsterdam.

Promotores
Prof JD van Buul PhD and prof APJ Vlaar MD PhD

Copromotor
R Kapur PhD

Venue
University of Amsterdam, Agnietenkapel (invitation only) and online

Summary

Acute Respiratory Distress Syndrome (ARDS) is a life-threatening condition where the alveoli fill with inflammatory cells and blood plasma (edema), impeding oxygen uptake and making it difficult to breathe. Severe inflammation and trauma cause ARDS, which ends in death in an estimated 40% of cases. Transfusion-Related Acute Lung Injury (TRALI) can lead to ARDS, but is a result of blood transfusion in two steps: (1) systemic underlying inflammation in the patient and (2), transfusion of biological response modifiers or matching antibodies to HLA and HNA. The exact mechanisms behind the pathologies are not yet clear and to date there is no effective treatment. ARDS and TRALI both have strong immunological profiles and result in destruction of the barrier between the blood circulation and lung tissue, which can result in long-term or permanent damage in survivors. Throughout the cardiovascular system, this barrier consists of so-called endothelial cells. Endothelial cells determine which plasma proteins and immune cells are allowed to pass from the blood to the tissue and actively counteract leakage during these processes. Endothelial cells are affected by signals from the rest of the body, such as blood pressure or stress signals from surrounding cells, which changes their barrier and signal function.
In this thesis, we have investigated various factors that can affect barrier function and trans-endothelial migration of immune cells in endothelial cells, to better understand when and how it becomes dysregulated, and where one can possibly intervene to counteract edema and damage in ARDS and TRALI.