Die Rolle der Thrombozyten in der Resolution von Leberentzündung und der Regeneration des Gewebes

01.07.2018 bis 30.06.2022

Hepatic ischaemia-reperfusion (I/R) injury is a major adverse consequence of liver transplantation, haemorrhagic shock, or extensive hepatic surgery and associated with a high mortality rate. The underlying pathomechanisms are incompletely understood and treatment options limited. The re-cruitment of activated leukocytes and a subsequent parenchymal injury are hallmarks of liver I/R. The prompt elimination of the disposed leukocytes is essential for the affected tissues to return to homeostasis. This resolution of inflammation is an active process coordinated by a complex regula-tory network of cells and mediators that ideally results in reconstituted organ function. Non-resolving inflammation can result in severe ongoing critical illness. Recent work has linked platelets with liver I/R injury, but their role is incompletely understood. Our preliminary data indicates a dual role of platelets in liver injury with a pro-inflammatory role in the early phase, but support of resolution at later time points. Using in vitro assays and human platelets and immune cells we will analyse how platelets modulate neutrophils and macrophages. We have established a platelet transfer protocol which allows us – in combination with transgenic mouse models – to specifically study the molecular pathways via which platelets modulate the resolution of liver I/R. This approach will be complement-ed by measurements of specialized lipid mediators (SPM). In addition we will perform confocal in-travital imaging (IVM), supported by histological analyses to map the cellular interactions following hepatic I/R. These studies will provide new insights into the pathomechanisms underlying sterile inflammation and resolution programmes in general.