Vitronectin promotes immunothrombotic dysregulation in the venular microvasculature.

Autor:	Uhl B; Department of Otorhinolaryngology, University Hospital, Ludwig-Maximilians-Universität München (LMU), Munich, Germany.; Walter Brendel Centre of Experimental Medicine, University Hospital, Ludwig-Maximilians-Universität München (LMU) Munich, Munich, Germany., Haring F; Department of Otorhinolaryngology, University Hospital, Ludwig-Maximilians-Universität München (LMU), Munich, Germany.; Walter Brendel Centre of Experimental Medicine, University Hospital, Ludwig-Maximilians-Universität München (LMU) Munich, Munich, Germany., Slotta-Huspenina J; Department of Pathology, Technical University of Munich, Munich, Germany., Luft J; Department of Otorhinolaryngology, University Hospital, Ludwig-Maximilians-Universität München (LMU), Munich, Germany.; Walter Brendel Centre of Experimental Medicine, University Hospital, Ludwig-Maximilians-Universität München (LMU) Munich, Munich, Germany., Schneewind V; Department of Otorhinolaryngology, University Hospital, Ludwig-Maximilians-Universität München (LMU), Munich, Germany.; Walter Brendel Centre of Experimental Medicine, University Hospital, Ludwig-Maximilians-Universität München (LMU) Munich, Munich, Germany., Hildinger J; Department of Otorhinolaryngology, University Hospital, Ludwig-Maximilians-Universität München (LMU), Munich, Germany.; Walter Brendel Centre of Experimental Medicine, University Hospital, Ludwig-Maximilians-Universität München (LMU) Munich, Munich, Germany., Wu Z; Department of Otorhinolaryngology, University Hospital, Ludwig-Maximilians-Universität München (LMU), Munich, Germany.; Walter Brendel Centre of Experimental Medicine, University Hospital, Ludwig-Maximilians-Universität München (LMU) Munich, Munich, Germany., Steiger K; Department of Pathology, Technical University of Munich, Munich, Germany., Smiljanov B; Department of Otorhinolaryngology, University Hospital, Ludwig-Maximilians-Universität München (LMU), Munich, Germany.; Walter Brendel Centre of Experimental Medicine, University Hospital, Ludwig-Maximilians-Universität München (LMU) Munich, Munich, Germany., Batcha AMN; Institute of Medical Data Processing, Biometrics, and Epidemiology (IBE), University Hospital, Ludwig-Maximilians-Universität München (LMU) Munich, Munich, Germany.; Data Integration for Future Medicine (DiFuture), University Hospital, Ludwig-Maximilians-Universität München (LMU) Munich, Munich, Germany., Keppler OT; Max von Pettenkofer Institute and Gene Center, Virology, National Reference Center for Retroviruses, Ludwig-Maximilians-Universität München (LMU) Munich, Munich, Germany.; German Centre for Infection Research (DZIF), Partner Site München, Munich, Germany., Hellmuth JC; Department of Medicine III, University Hospital, Ludwig-Maximilians-Universität München (LMU), Munich, Munich, Germany.; COVID-19 Registry of the LMU Munich (CORKUM), University Hospital, Ludwig-Maximilians-Universität München (LMU) Munich, Munich, Germany., Lahmer T; Department of Internal Medicine II, Technical University of Munich, Munich, Germany., Stock K; Department of Nephrology, Technical University of Munich, Munich, Germany., Weiss BG; Department of Otorhinolaryngology, University Hospital, Ludwig-Maximilians-Universität München (LMU), Munich, Germany., Canis M; Department of Otorhinolaryngology, University Hospital, Ludwig-Maximilians-Universität München (LMU), Munich, Germany., Stark K; Department of Cardiology, University Hospital, Ludwig-Maximilians-Universität München (LMU) Munich, Munich, Germany., Bromberger T; Institute of Experimental Hematology, Technical University of Munich, Munich, Germany., Moser M; Institute of Experimental Hematology, Technical University of Munich, Munich, Germany., Schulz C; Department of Cardiology, University Hospital, Ludwig-Maximilians-Universität München (LMU) Munich, Munich, Germany., Weichert W; Department of Pathology, Technical University of Munich, Munich, Germany., Zuchtriegel G; Department of Otorhinolaryngology, University Hospital, Ludwig-Maximilians-Universität München (LMU), Munich, Germany.; Walter Brendel Centre of Experimental Medicine, University Hospital, Ludwig-Maximilians-Universität München (LMU) Munich, Munich, Germany., Reichel CA; Department of Otorhinolaryngology, University Hospital, Ludwig-Maximilians-Universität München (LMU), Munich, Germany.; Walter Brendel Centre of Experimental Medicine, University Hospital, Ludwig-Maximilians-Universität München (LMU) Munich, Munich, Germany.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2023 Feb 08; Vol. 14, pp. 1078005. Date of Electronic Publication: 2023 Feb 08 (Print Publication: 2023).
DOI:	10.3389/fimmu.2023.1078005
Abstrakt:	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. Competing Interests: Author WW declarers the following conflict of interests: Research grants from Roche, MSD, BMS, and AstraZeneca. Advisory board, lectures, speaker bureaus: Roche, MSD, BMS, AstraZeneca, Pfizer, Merck, Lilly, Boehringer, Novartis, Takeda, Bayer, Janssen, Amgen, Astellas, Illumina, Eisai, Siemens, Agilent, ADC, GSK, and Molecular Health. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Uhl, Haring, Slotta-Huspenina, Luft, Schneewind, Hildinger, Wu, Steiger, Smiljanov, Batcha, Keppler, Hellmuth, Lahmer, Stock, Weiss, Canis, Stark, Bromberger, Moser, Schulz, Weichert, Zuchtriegel and Reichel.)
Databáze:	MEDLINE
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