Frontiers in Immunology (Feb 2023)
Vitronectin promotes immunothrombotic dysregulation in the venular microvasculature
- Bernd Uhl,
- Bernd Uhl,
- Florian Haring,
- Florian Haring,
- Julia Slotta-Huspenina,
- Joshua Luft,
- Joshua Luft,
- Vera Schneewind,
- Vera Schneewind,
- Jonas Hildinger,
- Jonas Hildinger,
- Zhengquan Wu,
- Zhengquan Wu,
- Katja Steiger,
- Bojan Smiljanov,
- Bojan Smiljanov,
- Aarif M. N. Batcha,
- Aarif M. N. Batcha,
- Oliver T. Keppler,
- Oliver T. Keppler,
- Johannes C. Hellmuth,
- Johannes C. Hellmuth,
- Tobias Lahmer,
- Konrad Stock,
- Bernhard G. Weiss,
- Martin Canis,
- Konstantin Stark,
- Thomas Bromberger,
- Markus Moser,
- Christian Schulz,
- Wilko Weichert,
- Gabriele Zuchtriegel,
- Gabriele Zuchtriegel,
- Christoph A. Reichel,
- Christoph A. Reichel
Affiliations
- Bernd Uhl
- Department of Otorhinolaryngology, University Hospital, Ludwig-Maximilians-Universität München (LMU), Munich, Germany
- Bernd Uhl
- Walter Brendel Centre of Experimental Medicine, University Hospital, Ludwig-Maximilians-Universität München (LMU) Munich, Munich, Germany
- Florian Haring
- Department of Otorhinolaryngology, University Hospital, Ludwig-Maximilians-Universität München (LMU), Munich, Germany
- Florian Haring
- Walter Brendel Centre of Experimental Medicine, University Hospital, Ludwig-Maximilians-Universität München (LMU) Munich, Munich, Germany
- Julia Slotta-Huspenina
- Department of Pathology, Technical University of Munich, Munich, Germany
- Joshua Luft
- Department of Otorhinolaryngology, University Hospital, Ludwig-Maximilians-Universität München (LMU), Munich, Germany
- Joshua Luft
- Walter Brendel Centre of Experimental Medicine, University Hospital, Ludwig-Maximilians-Universität München (LMU) Munich, Munich, Germany
- Vera Schneewind
- Department of Otorhinolaryngology, University Hospital, Ludwig-Maximilians-Universität München (LMU), Munich, Germany
- Vera Schneewind
- Walter Brendel Centre of Experimental Medicine, University Hospital, Ludwig-Maximilians-Universität München (LMU) Munich, Munich, Germany
- Jonas Hildinger
- Department of Otorhinolaryngology, University Hospital, Ludwig-Maximilians-Universität München (LMU), Munich, Germany
- Jonas Hildinger
- Walter Brendel Centre of Experimental Medicine, University Hospital, Ludwig-Maximilians-Universität München (LMU) Munich, Munich, Germany
- Zhengquan Wu
- Department of Otorhinolaryngology, University Hospital, Ludwig-Maximilians-Universität München (LMU), Munich, Germany
- Zhengquan Wu
- Walter Brendel Centre of Experimental Medicine, University Hospital, Ludwig-Maximilians-Universität München (LMU) Munich, Munich, Germany
- Katja Steiger
- Department of Pathology, Technical University of Munich, Munich, Germany
- Bojan Smiljanov
- Department of Otorhinolaryngology, University Hospital, Ludwig-Maximilians-Universität München (LMU), Munich, Germany
- Bojan Smiljanov
- Walter Brendel Centre of Experimental Medicine, University Hospital, Ludwig-Maximilians-Universität München (LMU) Munich, Munich, Germany
- Aarif M. N. Batcha
- Institute of Medical Data Processing, Biometrics, and Epidemiology (IBE), University Hospital, Ludwig-Maximilians-Universität München (LMU) Munich, Munich, Germany
- Aarif M. N. Batcha
- Data Integration for Future Medicine (DiFuture), University Hospital, Ludwig-Maximilians-Universität München (LMU) Munich, Munich, Germany
- Oliver T. Keppler
- Max von Pettenkofer Institute and Gene Center, Virology, National Reference Center for Retroviruses, Ludwig-Maximilians-Universität München (LMU) Munich, Munich, Germany
- Oliver T. Keppler
- German Centre for Infection Research (DZIF), Partner Site München, Munich, Germany
- Johannes C. Hellmuth
- Department of Medicine III, University Hospital, Ludwig-Maximilians-Universität München (LMU), Munich, Munich, Germany
- Johannes C. Hellmuth
- COVID-19 Registry of the LMU Munich (CORKUM), University Hospital, Ludwig-Maximilians-Universität München (LMU) Munich, Munich, Germany
- Tobias Lahmer
- 0Department of Internal Medicine II, Technical University of Munich, Munich, Germany
- Konrad Stock
- 1Department of Nephrology, Technical University of Munich, Munich, Germany
- Bernhard G. Weiss
- Department of Otorhinolaryngology, University Hospital, Ludwig-Maximilians-Universität München (LMU), Munich, Germany
- Martin Canis
- Department of Otorhinolaryngology, University Hospital, Ludwig-Maximilians-Universität München (LMU), Munich, Germany
- Konstantin Stark
- 2Department of Cardiology, University Hospital, Ludwig-Maximilians-Universität München (LMU) Munich, Munich, Germany
- Thomas Bromberger
- 3Institute of Experimental Hematology, Technical University of Munich, Munich, Germany
- Markus Moser
- 3Institute of Experimental Hematology, Technical University of Munich, Munich, Germany
- Christian Schulz
- 2Department of Cardiology, University Hospital, Ludwig-Maximilians-Universität München (LMU) Munich, Munich, Germany
- Wilko Weichert
- Department of Pathology, Technical University of Munich, Munich, Germany
- Gabriele Zuchtriegel
- Department of Otorhinolaryngology, University Hospital, Ludwig-Maximilians-Universität München (LMU), Munich, Germany
- Gabriele Zuchtriegel
- Walter Brendel Centre of Experimental Medicine, University Hospital, Ludwig-Maximilians-Universität München (LMU) Munich, Munich, Germany
- Christoph A. Reichel
- Department of Otorhinolaryngology, University Hospital, Ludwig-Maximilians-Universität München (LMU), Munich, Germany
- Christoph A. Reichel
- Walter Brendel Centre of Experimental Medicine, University Hospital, Ludwig-Maximilians-Universität München (LMU) Munich, Munich, Germany
- DOI
- https://doi.org/10.3389/fimmu.2023.1078005
- Journal volume & issue
-
Vol. 14
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
