Leukocyte diapedesis through the blood vessel wall and mechanisms that modulate integrin activation

    This project aims at elucidating the mechanisms that regulate and mediate leukocyte endothelial adhesion and transmigration through the vessel wall. We will investigate how the endothelial receptors CD99 and CD99L2 that bind to different ligands mediate different steps of leukocyte adhesion to and transmigration through endothelium and the basement membrane. In addition, we will analyze how platelets prevent bleeding during neutrophil extravasation.

    Research area: Endothelial cell biology

    Prof. Dr. rer. nat. Dietmar Vestweber

    Funding period: July 2012 - June 2020

    • Publications

      Original articles

      • Li YT, Goswami D, Follmer M, Artz A, Pacheco-Blanco M, Vestweber D. (2019) Blood flow guides sequential support on neutrophil arrest and diapedesis by PILR-beta1 and PILR-alpha. eLIFE Aug 6;8. pii: e47642.
      • Braun LJ, Zinnhardt M, Vockel M, Drexler HC, Peters K, Vestweber D. (2019) VE-PTP inhibition stabilizes endothelial junctions by activating FGD5. EMBO Rep. 20(7):e47046.
        Schwartz MA, Vestweber D, Simons M. (2018) A unifying concept in vascular health and disease. Science 360: 270-271.
      • Goswami D, März S, Li YT, Artz A, Schäfer K, Seelige R, Pacheco-Blanco M, Jing D, Bixel MG, Araki M, Araki K, Yamamura KI, Vestweber D (2017) Endothelial CD99 supports arrest of mouse neutrophils in venules and binds to neutrophil PILRs. Blood 129(13): 1811-1822. (doi:10.1182/blood-2016-08-733394)
      • Song J, Zhang X, Buscher K, Wang Y, Wang H, Di Russo J, Li L, Lütke-Enking S, Zarbock A, Stadtmann A, Striewski P, Wirth B, Kuzmanov I, Wiendl H, Schulte D, Vestweber D, Sorokin L (2017) Endothelial basement membrane Laminin 511 contributes to endothelial junctional tightness and thereby inhibits leukocyte transmigration. Cell Rep 18(5): 1256-1269. (doi: 10.1016/j.celrep.2016.12.092)
      • Artz A, Butz S, Vestweber D (2016) GDF-15 inhibits integrin activation and mouse neutrophil recruitment through the ALK-5/TGF-bRII heterodimer. Blood 128(4): 529-541. (doi:10.1182/blood-2016-01-696617) 
      • Kurz AR, Pruenster M, Rohwedder I, Schäfer K, Vestweber D, Haas R, Catz SD, Sperandio M. (2016) MST1-dependent vesicle trafficking regulates neutrophil transmigration through the vascular basement membrane. J. Clin. Invest. 126:4125-4139.
      • Frye M, Dierkes M, Küppers V, Vockel M, Tomm J, Zeuschner D, Roissant J, Zarbock A, Koh GY, Peters K, Nottebaum AF, Vestweber D (2015) Interfering with VE-PTP stabilizes endothelial junctions in vivo via Tie-2 in the absence of VE-cadherin. J Exp Med 212: 2267-2287.
      • Hillgruber C, Pöppelmann B, Weishaupt C, Steingräber AK, Wessel F, Berdel WE, Gessner JE, Ho-Tin-Noé B, Vestweber D, Goerge T*(2015) Blocking neutrophil diapedesis prevents hemorrhage during thrombocytopenia. J Exp Med 212: 1255-1266. (*equal contribution)
      • Seelige R, Natsch C, März S, Jing D, Frye M, Butz S, Vestweber D (2013) Cutting edge: Endothelial-specific gene ablation of CD99L2 impairs leukocyte extravasation in vivo. J Immunol 190: 892-896.

      Reviews

      • Goswami D, Vestweber D (2016) How leukocytes trigger opening and sealing of gaps in the endothelial barrier. F1000Research 5(F1000 Faculty Rev):2321 (doi: 10.12688/f1000research.9185.1) 
      • Vestweber D (2015) How leukocytes cross the vascular endothelium. Nat Rev Immunol 15: 692-704.

      Book articles

      • Dejana E, Vestweber D (2013) The Role of VE-cadherin in Vascular Morphogenesis and Permeability Control. In: The Molecular Biology of Cadherins. F. v. Roy, ed Elsevier, 116: 119-144.