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Prof. Dr.med. Markus Sperandio
The Sperandio lab investigates the molecular mechanisms of leukocyte recruitment using intravital microscopy and several static and dynamic in vitro assays. Leukocyte recruitment proceeds along a well-defined cascade of events starting with selectin-dependent leukocyte capture to and rolling along the vessel wall. During rolling, leukocytes get into intimate contact with the endothelium, which allows endothelial-bound chemokines to interact with specific chemokine-receptors on leukocytes. This in turn triggers the activation of integrins leading to firm arrest and transmigration into tissue. We are interested in all aspects of leukocyte recruitment during inflammation in vivo. This includes the role of posttranslational glycosylation on selectin ligand and chemokine-receptor function. Using different glycosyltransferase deficient mice, we have elucidated the crucial role of core 2 GlcNAcT, ST3Gal-IV, and also of a specific Golgi GDP-fucose-transporter (Slc35c1) on leukocyte rolling and adhesion in vivo. Recently, we have begun to work on a novel intravital microscopy model in the mouse embryo, which provides us with a powerful new tool to investigate the maturing immune system during development in different embryonic and extraembryonic compartments.
Contact: markus.sperandio@med.uni-muenchen.de
Members of the Sperandio Team

Postdocs:
Kristina Heinig, Dr. rer. nat (maternity leave)
Claudia Nussbaum, Dr. med.
Monika Prünster, Ph. D.
Ina Rohwedder, Dr. rer. nat.

Ph. D Students:
Roland Immler
Myriam Ripphahn

Medical Doctoral Students:
Christian David
Annamaria Florian
Tobias Steffen

Lab Technician:
Susanne Bierschenk
Nadine Schmidt

Coordinator Graduate Program of SFB914:
Verena Kochan, Dr. rer. nat.

Recent publications:

Kurz AR, Pruenster M, Rohwedder I, Ramadass M, Schäfer K, et al. MST1-dependent vesicle trafficking regulates neutrophil transmigration through the vascular basement membrane. J Clin Invest. 2016 Nov 1;126(11):4125-4139. PubMed PMID: 27701149; PubMed Central PMCID: PMC5096904.

Csépányi-Kömi R, Wisniewski É, Bartos B, Lévai P, Németh T, et al. Rac GTPase Activating Protein ARHGAP25 Regulates Leukocyte Transendothelial Migration in Mice. J Immunol. 2016 Oct 1;197(7):2807-15. PubMed PMID: 27566826.

Heinig K, Sperandio M. Interleukin-1R8: balancing inflammation and hemostasis in platelets. Cardiovasc Res. 2016 Sep;111(4):307-9. PubMed PMID: 27521812.

Mardahl M, Schröter MF, Engelbert D, Pink M, Sperandio M, et al. Core 2 ß1,6-N-acetylglucosaminyltransferase-I, crucial for P-selectin ligand expression is controlled by a distal enhancer regulated by STAT4 and T-bet in CD4+ T helper cells 1. Mol Immunol. 2016 Sep;77:132-40. PubMed PMID: 27505708.

Stark K, Philippi V, Stockhausen S, Busse J, Antonelli A, et al. Disulfide HMGB1 derived from platelets coordinates venous thrombosis in mice. Blood. 2016 Aug 29;PubMed PMID: 27574188.

Pruenster M, Vogl T, Roth J, Sperandio M. S100A8/A9: From basic science to clinical application. Pharmacol Ther. 2016 Aug 1;PubMed PMID: 27492899.

Ziegler T, Horstkotte M, Lange P, Ng J, Bongiovanni D, et al. Endothelial RAGE exacerbates acute postischaemic cardiac inflammation. Thromb Haemost. 2016 Aug 1;116(2):300-8. PubMed PMID: 27412300.

Klapproth S, Sperandio M, Pinheiro EM, Prünster M, Soehnlein O, et al. Loss of the Rap1 effector RIAM results in leukocyte adhesion deficiency due to impaired β2 integrin function in mice. Blood. 2015 Dec 17;126(25):2704-12. PubMed PMID: 26337492; PubMed Central PMCID: PMC4683331.

Klapproth S, Moretti FA, Zeiler M, Ruppert R, Breithaupt U, et al. Minimal amounts of kindlin-3 suffice for basal platelet and leukocyte functions in mice. Blood. 2015 Dec 10;126(24):2592-600. PubMed PMID: 26438512.

Kruse C, Kurz AR, Pálfi K, Humbert PO, Sperandio M, et al. Polarity Protein Scrib Facilitates Endothelial Inflammatory Signaling. Arterioscler Thromb Vasc Biol. 2015 Sep;35(9):1954-62. PubMed PMID: 26205961.

Ruppert R, Moser M, Sperandio M, Rognoni E, Orban M, et al. Kindlin-3-mediated integrin adhesion is dispensable for quiescent but essential for activated hematopoietic stem cells. J Exp Med. 2015 Aug 24;212(9):1415-32. PubMed PMID: 26282877; PubMed Central PMCID: PMC4548061.

Heinig K, Sage F, Robin C, Sperandio M. Development and trafficking function of haematopoietic stem cells and myeloid cells during fetal ontogeny. Cardiovasc Res. 2015 Aug 1;107(3):352-63. PubMed PMID: 25987546.

Wache C, Klein M, Ostergaard C, Angele B, Häcker H, et al. Myeloid-related protein 14 promotes inflammation and injury in meningitis. J Infect Dis. 2015 Jul 15;212(2):247-57. PubMed PMID: 25605866.

Pruenster M, Kurz AR, Chung KJ, Cao-Ehlker X, Bieber S, et al. Extracellular MRP8/14 is a regulator of β2 integrin-dependent neutrophil slow rolling and adhesion. Nat Commun. 2015 Apr 20;6:6915. PubMed PMID: 25892652; PubMed Central PMCID: PMC4411303.

Nussbaum C, Bannenberg S, Keul P, Gräler MH, Gonçalves-de-Albuquerque CF, et al. Sphingosine-1-phosphate receptor 3 promotes leukocyte rolling by mobilizing endothelial P-selectin. Nat Commun. 2015 Apr 2;6:6416. PubMed PMID: 25832730; PubMed Central PMCID: PMC4396399.

Wache C, Klein M, Ostergaard C, Angele B, Häcker H, Pfister HW, Pruenster M, Sperandio M, Leanderson T, Roth J, Vogl T, Koedel U. Myeloid‐Related Protein 14 Promotes Inflammation and Injury in Meningitis. J Infect Dis. 2015; 212(2):247‐57.

Chung KJ, Mitroulis I, Wiessner JR, Zheng YY, Siegert G, et al. A novel pathway of rapid TLR-triggered activation of integrin-dependent leukocyte adhesion that requires Rap1 GTPase. Mol Biol Cell. 2014 Oct 1;25(19):2948-55. PubMed PMID: 25057020; PubMed Central PMCID: PMC4230584.

Weckbach LT, Gola A, Winkelmann M, Jakob SM, Groesser L, et al. The cytokine midkine supports neutrophil trafficking during acute inflammation by promoting adhesion via β2 integrins (CD11/CD18). Blood. 2014 Mar 20;123(12):1887-96. PubMed PMID: 24458438.

Doring Y, Noels H, Mandl MM, Kramp B, Neideck C, Lievens D, Drechsler M, Megens RT, Tilstam PV, Langer M, Hartwig H, Theelen W, Marth JD, Sperandio M, Soehnlein O, Weber C. Deficiency of the Sialyltransferase St3Gal4 Reduces Ccl5-Mediated Myeloid Cell Recruitment and Arrest. Circ Res 2014 March 14;114(6):976-81.

Gonzalvo-Feo S, Del Prete A, Pruenster M, Salvi V, Wang L, Sironi M, Bierschenk S, Sperandio M, Vecchi A, Sozzani S. Endothelial Cell-Derived Chemerin Promotes Dendritic Cell Transmigration. J Immunol 2014 March 1; 192(5):2366-2373.

Schmidt S, Moser M, Sperandio M. The molecular basis of leukocyte recruitment and its deficiencies. Mol Immunol. 2013 August; 55(1):49-58.

Sperandio M, Hirsch E. Editorial to the SI Leukocyte Adhesion and Migration. Mol Immunol. 2013 August; 55(1):48.

Ziegler T, Horstkotte J, Schwab C, Pfetsch V, Weinmann K, Dietzel S, Rohwedder I, Hinkel R, Gross L, Lee S, Hu J, Soehnlein O, Franz WM, Sperandio M, Pohl U, Thomas M, Weber C, Augustin HG, Fässler R, Deutsch U, Kupatt C. Angiopoietin 2 mediates microvascular and hemodynamic alterations in sepsis. J Clin Invest. 2013 Jul 1.

Höhne C, Wenzel M, Angele B, Hammerschmidt S, Häcker H, Klein M, Bierhaus A, Sperandio M, Pfister HW, Koedel U. High mobility group box 1 prolongs inflammation and worsens disease in pneumococcal meningitis. Brain 2013 June; 136(Pt 6):1746-1759.

Stachel G, Trenkwalder T, Götz F, El Aouni C, Muenchmeier N, Pfosser A, Nussbaum C, Sperandio M, Hatzopoulos AK, Hinkel R, Nelson PJ, Kupatt C. SDF-1 fused to a fractalkine stalk and a GPI anchor enables functional neovascularization. Stem Cells, 31(9):1795-1805, June 6, 2013.

Sperandio M, Quackenbush EJ, Sushkova N, Altstätter J, Nussbaum C, Schmid S, Pruenster M, Kurz A, Margraf A, Steppner A, Schweiger N, Borsig L, Boros I, Krajewski N, Genzel-Boroviczeny O, Jeschke U, Frommhold D, von Andrian UH. Ontogenetic regulation of leukocyte recruitment in mouse yolk sac vessels. Blood 2013 May 23; 121(21):e118-128.

Jakob SM, Pick R, Brechtefeld D, Nussbaum C, Kiefer F, Sperandio M, Walzog B. Hematopoietic progenitor kinase 1 (HPK1) is required for LFA-1-mediated neutrophil recruitment during the acute inflammatory response. Blood 2013 May 16; 121(20):4184-4194

Nussbaum C, Klinke A, Adam M, Baldus S, Sperandio M. Myeloperoxidase - a leukocyte-derived protagonist of inflammation and cardiovascular disease. Antioxid.Redox.Signal 2012 February 20; 18(6):692-713.

Nussbaum C, Gloning A, Pruenster M, Frommhold D, Bierschenk S, Genzel-Boroviczény O, von Andrian UH, Quackenbush E, Sperandio M. Neutrophil and endothelial adhesive function during human fetal ontogeny. J Leukoc Biol 2013 February; 93(2):175-184

Yang WH, Nussbaum C, Grewal PK, Marth JD, Sperandio M. Coordinated Roles of ST3Gal-VI and ST3Gal-IV Sialyltransferases in the Synthesis of Selectin Ligands. Blood 2012 August 2; 120 (5):1015-1026.

Bodewits K, Sperandio M. Posttranslational sialylation and its impact on leukocyte recruitment during inflammation. SPR - Carbohydrate Chemistry: Chemical and Biological Approaches.  A. P. Rauter and T. Lindhorst. Anonymous. Royal Society of Chemistry. (38):75-93, 2012.

Fischer S, Grantzow T, Pagel JI, Tschernatsch M, Sperandio M, T. Preissner KT, Deindl E. Extracellular RNA promotes leukocyte recruitment in the vascular system by mobilising proinflammatory cytokines. Thromb.Haemost. 2012 July 20; 108 (4).

Hepper I, Schymeinsky J, Weckbach LT, Jakob SM, Frommhold D, Sixt M, Laschinger M, Sperandio M, Walzog B. The mammalian actin-binding protein 1 is critical for spreading and intraluminal crawling of neutrophils under flow conditions. J.Immunol. 2012 May 1; 188 (9):4590-4601.

Sperandio M. The expanding role of alpha2-3 sialylation for leukocyte trafficking in vivo. Ann.N.Y.Acad.Sci. 2012 April; 1253:201-205.

Frommhold D, Kamphues A, Dannenberg S, Buschmann K, Zablotskaya V, Tschada R, Lange-Sperandio B, Nawroth PP, Poeschl J, Bierhaus A, Sperandio M. RAGE and ICAM-1 differentially control leukocyte recruitment during acute inflammation in a stimulus-dependent manner. BMC.Immunol. 2011October 4; 12:56.

Frommhold D, Tschada J, Braach N, Buschmann K, Doerner A, Pflaum J, Stahl M, Wang H, Koch L, Sperandio M, Bierhaus A, Isermann B, Poeschl J. Protein C Concentrate Controls Leukocyte Recruitment during Inflammation and Improves Survival during Endotoxemia after Efficient in Vivo Activation. Am.J.Pathol. 2011 September 8; 179(5):2637-50.

Gambardella L, Anderson KE, Nussbaum C, Segonds-Pichon A, Margarido T, Norton L, Ludwig T, Sperandio M, Hawkins PT, Stephens L, Vermeren S. The GTPase-activating protein ARAP3 regulates chemotaxis and adhesion-dependent processes in neutrophils. Blood 2011 July 28; 118(4):1087-98.

Nussbaum C, Sperandio M. Innate immune cell recruitment in the fetus and neonate. J Reprod Immunol 2011 June; 90(1):74-81.

Schymeinsky J, Sperandio M, Walzog B. The mammalian actin-binding protein 1 (mAbp1): a novel molecular player in leukocyte biology. Trends Cell Biol 2011 April; 21(4):247-55.

Klinke*, C. Nussbaum*, L. Kubala, K. Friedrichs, T.K. Rudolph, V. Rudolph, H.-J. Paust, C. Schröder, D. Benten, D. Lau, K. Szocs, P.G. Furtmüller, P. Heeringa, K. Sydow, H.-J. Duchstein, H. Ehmke, U. Schumacher, T. Meinertz, M. Sperandio and S. Baldus. Myeloperoxidase attracts neutrophils by physical forces. Blood. 2011 January 27; 117:1350-1358. (*equal contribution)

Frommhold D, Kamphues A, Mannigel I, Pruenster M, Lukic IK, Socher I, Zablotskaya V, Buschmann K, Lange-Sperandio B, Schymeinsky J, Ryschich E, Poeschl J, Kupatt C, Nawroth P, Walzog B, Bierhaus A, Sperandio M. RAGE and ICAM-1 cooperate in mediating leukocyte recruitment during acute inflammation in vivo. Blood 2010 August 5; 116(5):841-9.

Nussbaum C, Moser M, Sperandio M. Leukocyte adhesion deficiency-III: when leukocytes cannot stop. Pediatr Res 2010 April; 67(4):339.

Pfosser A, El-Aouni C, Pfisterer I, Dietz M, Globisch F, Stachel G, Trenkwalder T, Pinkenburg O, Horstkotte J, Hinkel R, Sperandio M, Hatzopoulos AK, Boekstegers P, Bals R, Kupatt C. NF kappaB Activation in Embryonic Endothelial Progenitor Cells Enhances Neovascularization Via PSGL-1 Mediated Recruitment: Novel Role for LL37. Stem Cells 2010 February 1; 28(2):376-85.

Marcos V, Nussbaum C, Vitkov L, Hector A, Wiedenbauer AM, Roos D, Kuijpers TW, Krautgartner WD, Genzel-Boroviczeny O, Sperandio M, and Hartl D. Delayed but functional neutrophil extracellular trap formation in neonates. Blood 2009 November 26; 114:4908-4911.

Dillmann F, Veldwijk MR, Laufs S, Sperandio M, Calandra G, Wenz F, Zeller WJ, Fruehauf S, Dillmann F, Veldwijk MR, Laufs S, Sperandio M, Calandra G, Wenz F, Zeller WJ, Fruehauf S. Plerixafor inhibits chemotaxis toward SDF-1 and CXCR4-mediated stroma contact in a dose-dependent manner resulting in increased susceptibility of BCR-ABL(+) cell to Imatinib and Nilotinib. Leuk Lymphoma 2009 October; 50(10):1676-86.

Schymeinsky J, Gerstl R, Mannigel I, Niedung K, Frommhold D, Panthel K, Heesemann J, Sixt M, Quast T, Kolanus W, Mocsai A, Wienands J, Sperandio M, Walzog B. A fundamental role of mAbp1 in neutrophils: impact on beta(2) integrin-mediated phagocytosis and adhesion in vivo. Blood 2009 July 28; 114(19):4209-20.

Sperandio M, Gleissner CA, Ley K. Glycosylation in immune cell trafficking. Immunol Rev 2009 July; 230(1):97-113.

Ryschich E, Kerkadze V, Deduchovas O, Salnikova O, Parseliunas A, Marten A, Hartwig W, Sperandio M, Schmidt J. Intracapillary leukocyte accumulation as a novel antihemorrhagic mechanism in acute pancreatitis in mice. Gut 2009 May 20; 58(11):1508-1516.

Jakus Z, Simon E, Frommhold D, Sperandio M, Mocsai A. Critical role of phospholipase Cgamma2 in integrin and Fc receptor-mediated neutrophil functions and the effector phase of autoimmune arthritis. J Exp Med 2009 March 16; 206(3):577-93.

Moser M, Bauer M, Schmid S, Ruppert R, Schmidt S, Sixt M, Wang HV, Sperandio M, Fassler R. Kindlin-3 is required for beta2 integrin-mediated leukocyte adhesion to endothelial cells. Nat Med 2009 March; 15(3):300-5.

Yakubenia S, Frommhold D, Scholch D, Hellbusch CC, Korner C, Petri B, Jones C, Ipe U, Bixel MG, Krempien R, Sperandio M, Wild MK. Leukocyte trafficking in a mouse model for leukocyte adhesion deficiency II/congenital disorder of glycosylation IIc. Blood 2008 August 15; 112(4):1472-81.

Frommhold D, Ludwig A, Bixel MG, Zarbock A, Babushkina I, Weissinger M, Cauwenberghs S, Ellies LG, Marth JD, Beck-Sickinger AG, Sixt M, Lange-Sperandio B, Zernecke A, Brandt E, Weber C, Vestweber D, Ley K, Sperandio M. Sialyltransferase ST3Gal-IV controls CXCR2-mediated firm leukocyte arrest during inflammation. J Exp Med 2008 June 9; 205(6):1435-46.

Hellbusch CC, Sperandio M, Frommhold D, Yakubenia S, Wild MK, Popovici D, Vestweber D, Grone HJ, von FK, Lubke T, Korner C. Golgi GDP-fucose transporter-deficient mice mimic congenital disorder of glycosylation IIc/leukocyte adhesion deficiency II. J Biol Chem 2007 February 2; 282(14):10762-72.

Zernecke A, Bot I, Djalali-Talab YD, Shagdarsuren E, Bidzhekov K, Meiler S, Krohn R, Schober A, Sperandio M, Soehnlein O, Bornemann J, Tacke F, Biessen EA, Weber C. Protective role of CXC receptor 4/CXC ligand 12 unveils the importance of neutrophils in atherosclerosis. Circ Res 2008 February 1; 102(2):209-17.

Frommhold D, Mannigel I, Schymeinsky J, Mocsai A, Poeschl J, Walzog B, Sperandio M. Spleen tyrosine kinase Syk is critical for sustained leukocyte adhesion during inflammation in vivo. BMC Immunol 2007; 8:31.

Lange-Sperandio B, Sperandio M, Nawroth P, Bierhaus A. RAGE signaling in cell adhesion and inflammation. Curr Ped Rev 2007; 3(1):1-9.