2. Academic Validation
  3. Vitronectin promotes immunothrombotic dysregulation in the venular microvasculature

Vitronectin promotes immunothrombotic dysregulation in the venular microvasculature

  • Front Immunol. 2023 Feb 8;14:1078005. doi: 10.3389/fimmu.2023.1078005.
Bernd Uhl 1 2,  Florian Haring 1 2,  Julia Slotta-Huspenina 3,  Joshua Luft 1 2,  Vera Schneewind 1 2,  Jonas Hildinger 1 2,  Zhengquan Wu 1 2,  Katja Steiger 3,  Bojan Smiljanov 1 2,  Aarif M N Batcha 4 5,  Oliver T Keppler 6 7,  Johannes C Hellmuth 8 9,  Tobias Lahmer 10,  Konrad Stock 11,  Bernhard G Weiss 1,  Martin Canis 1,  Konstantin Stark 12,  Thomas Bromberger 13,  Markus Moser 13,  Christian Schulz 12,  Wilko Weichert 3,  Gabriele Zuchtriegel 1 2,  Christoph A Reichel 1 2
Affiliations

Affiliations

  • 1 Department of Otorhinolaryngology, University Hospital, Ludwig-Maximilians-Universität München (LMU), Munich, Germany.
  • 2 Walter Brendel Centre of Experimental Medicine, University Hospital, Ludwig-Maximilians-Universität München (LMU) Munich, Munich, Germany.
  • 3 Department of Pathology, Technical University of Munich, Munich, Germany.
  • 4 Institute of Medical Data Processing, Biometrics, and Epidemiology (IBE), University Hospital, Ludwig-Maximilians-Universität München (LMU) Munich, Munich, Germany.
  • 5 Data Integration for Future Medicine (DiFuture), University Hospital, Ludwig-Maximilians-Universität München (LMU) Munich, Munich, Germany.
  • 6 Max von Pettenkofer Institute and Gene Center, Virology, National Reference Center for Retroviruses, Ludwig-Maximilians-Universität München (LMU) Munich, Munich, Germany.
  • 7 German Centre for Infection Research (DZIF), Partner Site München, Munich, Germany.
  • 8 Department of Medicine III, University Hospital, Ludwig-Maximilians-Universität München (LMU), Munich, Munich, Germany.
  • 9 COVID-19 Registry of the LMU Munich (CORKUM), University Hospital, Ludwig-Maximilians-Universität München (LMU) Munich, Munich, Germany.
  • 10 Department of Internal Medicine II, Technical University of Munich, Munich, Germany.
  • 11 Department of Nephrology, Technical University of Munich, Munich, Germany.
  • 12 Department of Cardiology, University Hospital, Ludwig-Maximilians-Universität München (LMU) Munich, Munich, Germany.
  • 13 Institute of Experimental Hematology, Technical University of Munich, Munich, Germany.
PMID: 36845099 DOI: 10.3389/fimmu.2023.1078005
Abstract

Microvascular immunothrombotic dysregulation is a critical process in the pathogenesis of severe systemic inflammatory diseases. The mechanisms controlling immunothrombosis in inflamed microvessels, however, remain poorly understood. Here, we report that under systemic inflammatory conditions the matricellular glycoproteinvitronectin (VN) establishes an intravascular scaffold, supporting interactions of aggregating platelets with immune cells and the venular endothelium. Blockade of the VN receptor glycoprotein (GP)IIb/IIIa interfered with this multicellular interplay and effectively prevented microvascular clot formation. In line with these experimental data, particularly VN was found to be enriched in the pulmonary microvasculature of patients with non-infectious (pancreatitis-associated) or infectious (coronavirus disease 2019 (COVID-19)-associated) severe systemic inflammatory responses. Targeting the VN-GPIIb/IIIa axis hence appears as a promising, already feasible strategy to counteract microvascular immunothrombotic dysregulation in systemic inflammatory pathologies.

Keywords

SIRS; immunothrombosis; microvasculature; neutrophils; platelets; systemic inflammation; vitronectin.

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