Tension in the Tunnel Endothelial architecture and signalling during leukocyte extravasation

The vasculature system consists of a vast network of differently sized vessels that transport blood, essential nutrients and oxygen to all corners of the body. The innermost lining of all of these vessels is a monolayer of endothelial cells; the endothelium. In addition to facilitating the exchange of nutrients and gasses to and from all tissues in the body, the endothelium has a vital function in the immune system. Upon inflammation, the endothelium transmits signals of inflammation or cellular damage to the immune system, attracting circulating immune cells; the leukocytes. These leukocytes have to exert their function of clearing pathogens or dead cells in the tissues underlying the vessels, which they can only reach by traversing the endothelium. This means that the endothelium has to be a tight barrier, leakage of blood from the vessels is of course unwanted, but at the same time it has to facilitate the passage of leukocytes, while still maintaining its barrier properties. This thesis explores how the endothelial cells orchestrates the efficient and leak free passage of leukocytes from the vessels to the underlying tissues.