Mechanisms of leukocyte penetration of vascular cell basement membranes

    We investigate how the endothelial basement membrane (BM) acts as a barrier to leukocyte extravasation, focusing on the laminin isoforms (laminin 411 and laminin 511). Our studies highlight the endothelial BM as a hitherto underestimated niche for modulation of phenotypes of immune cells en route into inflamed tissues, and demonstrate that the effects of BM laminins differ depending on immune cell type. Different molecular mechanisms have been described and a laminin reporter mouse has been generated. Future experiments will permit distinction between mechanical and molecular information imparted by the endothelial BM on extravasating leukocytes of different types.


    Research area: Matrix biology, immunology

    Prof. Dr. Lydia Sorokin (PhD)

    Funding period: July 2012 - June 2024

    • Publications

      Original articles

      • Hallmann R, Hannocks MJ, Song J, Zhang X, Di Russo J, Luik AL, Burmeister M, Gerwien H, Sorokin L (2020) The role of basement membrane laminins in vascular function. Int. J. Biochem. Cell Biol 105823
      • Masthoff M, Gran S, Zhang X, Wachsmuth L, Bietenbeck M, Helfen A, Heindel W, Sorokin L, Roth J, Eisenblätter M, Wildgruber M, Faber C (2019) Temporal window for detection of inflammatory disease using dynamic cell tracking with time-lapse MRI. Scientific Rep. 8:9563.
      • Breuer J, Korpos E, Hannocks M-J, Schneider-Hohendorf T, Song J, Zondler L, Herich S, Flanagan K, Korn T, Zarbock A, Kuhlmann T, Sorokin L, Wiendl H, Schwab N. Blockade of MCAM/CD146 impedes CNS infiltration of T cells over the choroid plexus. J Neuroinflamm 2018. 15, 236-248.
      • Masthoff M, Gran S, Zhang X, Wachsmuth L, Bietenbeck M, Helfen A, Heindel W, Sorokin L, Roth J, Eisenblätter M, Wildgruber M, Faber C. Temporal  window for detection of inflammatory disease using dynamic cell tracking with time-lapse MRI. Sci Rep 2018. 8, 9563.
      • Samus M, Seelige R, Schäfer K, Sorokin L, Vestweber D. CD99L2 deficiency inhibits leukocyte entry into the central nervous system and ameliorates neuroinflammation. J Leuko Biol 2018. 104, 787-797.
      • Di Russo J, Luik A-L, Yousif L, Oberleithner H, Hofschröer V, Klingauf J, van Bavel E, Bakker E NTP, Hellstrand P, Bhattachariya A, Albinsson S, Pincet F, Hallmann R, Sorokin L. Endothelial basement membrane laminin 511 is essential for shear stress response. EMBO J 2017. 36, 183-201.
      • Song J, Büscher K, Zhang X, Wang Y, Wang H, Di Russo J, Li L, Ludke-Enking S, Zarbock A, Stadtmann A, Striewski P, Wirth B, Kurmanov I, Wiendl H, Schulte D, Vestweber D, Sorokin L. Endothelial basement membrane laminin 511 contributes to endothelial junctional tightness and thereby inhibits leukocyte transmigration. Cell Rep 2017. 18: 1256-1269.
      • Buscher K, Wang H, Zhang X, Striewski P, Wirth B, Saggu G, Lütke-Enking S, Mayadas TN, Ley K, Sorokin L, Song J (2016) Protection from septic peritonitis by rapid neutrophil recruitment through omental high endothelial venules. Nat Commun. 2016 Mar 4;7:10828. doi: 10.1038/ncomms10828.
      • Hallmann R, Zhang X, Di Russo J, Li L, Song J, Hannocks M-J, Sorokin L (2015) The regulation of immune cell trafficking by the extracellular matrix. Curr Opin Cell Biol 36: 54-61.
      • Liu Z, Xu Y, Zhang X, Song J, Sorokin L, Bähler M (2015) The motorized RhoGAP myosin IXb (Myo9b) in leukocytes regulates experimental autoimmune encephalomyelitis induction and recovery. J Neuroimmunol 282: 25-32.
      • Song J, Wu C, Agrawal S, Korpos E, Wang Y, Faber C, Schäfers M, Körner H, Opdenakker G, Hallmann R, Sorokin L (2015) Focal MMP-2 and MMP-9 activity at the blood-brain barrier (BBB) promotes chemokine-induced leukocyte migration. Cell Reports 10 (7): 1040-1054. [doi: 10.1016/j.celrep.2015.01.037] Epub 2015 Feb 19.
      • Song J, Wu C, Zhang X, Sorokin L (2013) In vivo processing of CXCL5 (LIX) by matrix metalloproteinase (MMP)-2 and MMP-9 promotes early neutrophil recruitment in IL-1?-induced peritonitis. J Immunol 190: 401-410.
      • Zhang X, Wu C, Jian Song, Götte M, Sorokin L (2013) Syndecan-1, a cell surface proteoglycan, negatively regulates initial leukocyte recruitment to the brain across the choroid plexus in murine experimental autoimmune encephalomyelitis. J Immunol 191: 4551-4561


      • Di Russo J, Hannocks MJ, Luik AL, Song J, Zhang X, Yousif L, Aspite G, Hallmann R, Sorokin L (2016) Vascular laminins in physiology and pathology. Matrix Biol pii: S0945-053X(16)30102-0. (doi: 10.1016/j.matbio.2016.06.008. [Epub ahead of print])
      • Bogdani, M., Korpos, E., Simeonovic, C. J., Sorokin, L. and Wright, T. N. (2014). Extracellular matrix components in the pathogenesis of type 1 diabetes. Curr. Diab. Rep. 14, 552-564.