B.2: Regulation of Vascular Permeability and Leukocyte Extravasation
Participants: Dietmar Vestweber, Timo Betz, Cornelia Denz, Johannes Eble, Rupert Hallmann, Hans Oberleithner, Lydia Sorokin, Angela Stevens, Hans-Joachim Schnittler, Jan Vahrenhold, Benedikt Wirth, Alexander Zarbock
The endothelium and the underlying BM represent tightly regulated barriers for soluble molecules and cells, allowing recruitment of specific leukocyte populations during inflammation. Capturing of leukocytes at the endothelial surface requires the activation of leukocyte integrins, a process that has been shown to provide new options for the interference with inflammatory processes. Understanding the molecular mechanisms that control endothelial cell contact stability is a prerequisite for antagonizing pathological hyperpermeability and is also central for establishing ways to block the recruitment of leukocytes into inflammatory sites. The molecular composition of the underlying BM also contributes to determining where leukocytes pass through this barrier and elucidating how certain components of the BM facilitate or prevent transmigration will be an important future goal. Visualization of leukocyte emigration in transgenic mice by intravital fast live-confocal and 2-photon microscopy combined with mathematical models of 3D leukocyte tracking will be used to directly analyse leukocyte emigration. These studies will be complemented by biophysical techniques applied in vitro and ex vivo, and mathematical modelling and prediction of 2D and 3D leukocyte adhesion and migration due to chemotactic and/or localized signals. The aim of this project is to elucidate the molecular mechanisms that control vascular permeability and leukocyte extravasation.