The Weibel-Palade body From formation to fireworks

The inner lining of the vasculature is composed of a monolayer of endothelial cells (ECs), forming a dynamic barrier at the interface of the blood and the underlying tissue. In the frontline, ECs need to adequately respond to stress signals, ensure hemostasis, and regulate immune responses and angiogenesis. For this purpose they make the Weibel-Palade body (WPB): a unique, rod-shaped secretory granule that stores hemostatic, inflammatory and angiogenic mediators, which can be rapidly released into the blood upon vascular injury. The main component Von Willebrand Factor (VWF) is a large multimeric protein that plays a central role in hemostasis, and is required for WPB biogenesis. When secreted upon stimulation VWF multimers unwind, forming adhesive strings to catch platelets and promote thrombus formation. Qualitative or quantitative defects in VWF can lead to the bleeding disorder Von Willebrand’s disease (VWD). In this thesis we have studied the regulatory processes involved in WPB formation and trafficking and their impact on VWF secretion. The immunofluorescent imaging of VWF from formation until secretion exposes remarkable snapshots, reminiscent of microscopic fireworks, which have been the inspiration for the title.