Leukocyte migration through the blood vessel wall and mechanisms that modulate fluid passage across a specialized endothelium

    This proposal consists of two parts which aim at different endothelial barriers. The first part will focus on leukocyte extravasation. In detail, we will analyze mechanims that control chemotaxis and intra- and extravasacular crawling of leukocytes. In the second part, we will analyze the endothelial barrier of a specialized vessel in the eye, the Schlemm’s canal. We will investigate how the phosphatase VE-PTP regulates the uptake of aqueous humor from the eye, a task which is essential to prevent a build up of intraocular pressure and the development of glaucoma.

    Research area: Endothelial cell biology

    Prof. Dr. rer. nat. Dietmar Vestweber

    Funding period: July 2012 - June 2024

    • Publications

      Original articles

      • Samus M, Li YT, Sorokin L, Rottner K, Vestweber D (2020) Actin-Binding Protein Cortactin Promotes Pathogenesis of Experimental Autoimmune Encephalomyelitis by Supporting Leukocyte Infiltration into the Central Nervous System. J Neurosci 40(7):1389-1404
      • Rezaei M, Martins Cavaco AC, Stehling M, Nottebaum A, Brockhaus K, Caliandro MF, Schelhaas S, Schmalbein F, Vestweber D, Eble JA (2020) Extracellular Vesicle Transfer from Endothelial Cells Drives VE-Cadherin Expression in Breast Cancer Cells, Thereby Causing Heterotypic Cell Contacts. Cancers (Basel) 12(8):2138
      • Margraf A, Germena G, Drexler HCA, Rossaint J, Ludwig N, Prystaj B, Mersmann S, Thomas K, Block H, Gottschlich W, Liu C, Krenn PW, Haller H, Heitplatz B, Meyer Zu Brickwedde M, Moser M, Vestweber D, Zarbock A (2020) The integrin-linked kinase is required for chemokine-triggered high-affinity conformation of the neutrophil β2-integrin LFA-1. Blood 5;136(19):2200-2205
      • Li G, Nottebaum AF, Brigell M, Nevaro ID, Ipe U, Soldo B, Pakola S, Peters KG, Vestweber D, Stamer D (2020) A small molecule Tie2 activator, AKB-9778, reduces intraocular pressure by targeting VE-PTP in Schlemm’s Canal. Invest Ophtalmol Vis Sci 61(14):12
      • Braun LJ, Stegmeyer R, Schäfer K, Volkery S, Currie SM, Kempe B, Nottebaum AF, Vestweber D (2020) Platelets docking to VWF prevent leaks during leukocyte extravasation by stimulating Tie-2. Blood 136(5): 627-639
      • Bergerhausen L, Grosche J, Meissner J, Hecker C, Caliandro MF, Westerhausen C, Kamenac A, Rezaei M, Morgelin M, Poschmann G, Vestweber D, Hanschmann EM, Eble JA(2020) Extracellular Redox Regulation of a7b1 Integrin-Mediated Cell Migration Is Signaled via a Dominant Thiol-Switch. Antioxidants (Basel) 9 10.3390/antiox9030227
      • Arif N, Zinnhardt M, Nyamay’Antu A, Teber D, Brückner R, Schäfer K, Li Y-T, Trappmann B, Grashoff C, Vestweber D (2020) PECAM-1 supports diapedesis by tension-dependent dephosphorylation of VE-cadherin. EMBO J 3;40(9): e106113
      • 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.


      • 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.