Group Leader: Guttorm Haraldsen, M.D.Ph.D.Vascular endothelial cells line the inside of blood vessels. Once activated, they follow different programs, either getting sticky and recruiting leukocytes to sites of inflammation, or leaving the vessels themselves to build new blood levels. We focus on molecular mechanisms of endothelial cells differentiation with special emphasis on properties that enable leukocyte recruitment in immunity and inflammation, as well as those that enable vascular morphogenesis. |
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The current model of leukocyte adhesion to the vascular wall is viewed as a multi-step adhesion pathway. Chemokines presented at the endothelial cell surface enable the transition of leukocyte behaviour from rolling to firm adhesion, and are the focus of interest because they attract different subclasses of leukocytes. At sites of acute injury, leukocyte recruitment can occur rapidly, partly explained by the fact that endothelial cells store and rapidly release preformed chemokines to the vascular surface upon exposure to histamine or thrombin. We are currently studying the sorting profile of different chemokines in endothelial cells and the molecular mechanisms of their sorting.To understand the biology of endothelial cells in different vascular segments and organs we compare the gene expression profile of endothelial cells of different tissue origins, having identified the first nuclear factor of a specialized subtype of vascular endothelial cells (NF-HEV), the characterization of which is ongoing. In a different approach to understanding of vascular differentiation, we also developed a model for the adoptive transfer of endothelial cells. This technique is based on transferring single human endothelial cells to subcutaneous gels in immunodeficient mice in which they assemble to complex, functional vessels that make xenogeneic contact with the murine vascular system. Importantly, phenotypic properties that are lost in vitro are partly regained upon transfer, and by means of local, osmotic pump-delivery of soluble mediators to these gels, our method is a powerful tool for exploring the regulation of endothelial differentiation through direct experimental manipulation in vivo . |
