Thesis Janine Arts

Summary

During the inflammatory response, the white blood cells must exit the blood vessels at the right site to migrate into the tissue. To do so, the blood vessel wall cells – endothelial cells – provide signals when an inflammation in the underlying tissue occurs. The circulating white blood cells recognize these signals by interacting with the endothelial cells of the blood vessel wall. As inflammation often occurs in the underlying tissue, white blood cells maneuver out of the blood vessel, without causing excessive leakage of other blood components. Therefore, a tightly regulated interplay occurs when the white blood cells squeeze themselves between and through the endothelial cells. This process is called transendothelial migration; the migration of white blood cells through (trans) the blood vessel wall (endothelial layer). This process is tightly regulated to make it highly efficient. In this thesis new insights in the process of transendothelial migration are discussed. We describe a phenomenon called transendothelial migration hotspots. These preferred diapedesis sites are marked by adhesion molecules but also by endothelial membrane protrusions that are used by neutrophils to exit the vasculature. Furthermore, we discuss the post-diapedesis phase, where neutrophils migrate around focal adhesions underneath the endothelium. These new insights might help us better understanding TEM but also reveal targets for therapeutic intervention in disease situations.