Vitronectin promotes immunothrombotic dysregulation in the venular microvasculature
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 ma...
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Frontiers Media S.A.
2023-02-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1078005/full |
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| author | 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 |
| author_facet | 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 |
| author_sort | Bernd Uhl |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-10T16:34:51Z |
| format | Article |
| id | doaj.art-ade407ee878a42518dbdd312efef54f7 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-10T16:34:51Z |
| publishDate | 2023-02-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj.art-ade407ee878a42518dbdd312efef54f72023-02-08T13:51:21ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-02-011410.3389/fimmu.2023.10780051078005Vitronectin promotes immunothrombotic dysregulation in the venular microvasculatureBernd Uhl0Bernd Uhl1Florian Haring2Florian Haring3Julia Slotta-Huspenina4Joshua Luft5Joshua Luft6Vera Schneewind7Vera Schneewind8Jonas Hildinger9Jonas Hildinger10Zhengquan Wu11Zhengquan Wu12Katja Steiger13Bojan Smiljanov14Bojan Smiljanov15Aarif M. N. Batcha16Aarif M. N. Batcha17Oliver T. Keppler18Oliver T. Keppler19Johannes C. Hellmuth20Johannes C. Hellmuth21Tobias Lahmer22Konrad Stock23Bernhard G. Weiss24Martin Canis25Konstantin Stark26Thomas Bromberger27Markus Moser28Christian Schulz29Wilko Weichert30Gabriele Zuchtriegel31Gabriele Zuchtriegel32Christoph A. Reichel33Christoph A. Reichel34Department of Otorhinolaryngology, University Hospital, Ludwig-Maximilians-Universität München (LMU), Munich, GermanyWalter Brendel Centre of Experimental Medicine, University Hospital, Ludwig-Maximilians-Universität München (LMU) Munich, Munich, GermanyDepartment of Otorhinolaryngology, University Hospital, Ludwig-Maximilians-Universität München (LMU), Munich, GermanyWalter Brendel Centre of Experimental Medicine, University Hospital, Ludwig-Maximilians-Universität München (LMU) Munich, Munich, GermanyDepartment of Pathology, Technical University of Munich, Munich, GermanyDepartment of Otorhinolaryngology, University Hospital, Ludwig-Maximilians-Universität München (LMU), Munich, GermanyWalter Brendel Centre of Experimental Medicine, University Hospital, Ludwig-Maximilians-Universität München (LMU) Munich, Munich, GermanyDepartment of Otorhinolaryngology, University Hospital, Ludwig-Maximilians-Universität München (LMU), Munich, GermanyWalter Brendel Centre of Experimental Medicine, University Hospital, Ludwig-Maximilians-Universität München (LMU) Munich, Munich, GermanyDepartment of Otorhinolaryngology, University Hospital, Ludwig-Maximilians-Universität München (LMU), Munich, GermanyWalter Brendel Centre of Experimental Medicine, University Hospital, Ludwig-Maximilians-Universität München (LMU) Munich, Munich, GermanyDepartment of Otorhinolaryngology, University Hospital, Ludwig-Maximilians-Universität München (LMU), Munich, GermanyWalter Brendel Centre of Experimental Medicine, University Hospital, Ludwig-Maximilians-Universität München (LMU) Munich, Munich, GermanyDepartment of Pathology, Technical University of Munich, Munich, GermanyDepartment of Otorhinolaryngology, University Hospital, Ludwig-Maximilians-Universität München (LMU), Munich, GermanyWalter Brendel Centre of Experimental Medicine, University Hospital, Ludwig-Maximilians-Universität München (LMU) Munich, Munich, GermanyInstitute of Medical Data Processing, Biometrics, and Epidemiology (IBE), University Hospital, Ludwig-Maximilians-Universität München (LMU) Munich, Munich, GermanyData Integration for Future Medicine (DiFuture), University Hospital, Ludwig-Maximilians-Universität München (LMU) Munich, Munich, GermanyMax von Pettenkofer Institute and Gene Center, Virology, National Reference Center for Retroviruses, Ludwig-Maximilians-Universität München (LMU) Munich, Munich, GermanyGerman Centre for Infection Research (DZIF), Partner Site München, Munich, GermanyDepartment of Medicine III, University Hospital, Ludwig-Maximilians-Universität München (LMU), Munich, Munich, GermanyCOVID-19 Registry of the LMU Munich (CORKUM), University Hospital, Ludwig-Maximilians-Universität München (LMU) Munich, Munich, Germany0Department of Internal Medicine II, Technical University of Munich, Munich, Germany1Department of Nephrology, Technical University of Munich, Munich, GermanyDepartment of Otorhinolaryngology, University Hospital, Ludwig-Maximilians-Universität München (LMU), Munich, GermanyDepartment of Otorhinolaryngology, University Hospital, Ludwig-Maximilians-Universität München (LMU), Munich, Germany2Department of Cardiology, University Hospital, Ludwig-Maximilians-Universität München (LMU) Munich, Munich, Germany3Institute of Experimental Hematology, Technical University of Munich, Munich, Germany3Institute of Experimental Hematology, Technical University of Munich, Munich, Germany2Department of Cardiology, University Hospital, Ludwig-Maximilians-Universität München (LMU) Munich, Munich, GermanyDepartment of Pathology, Technical University of Munich, Munich, GermanyDepartment of Otorhinolaryngology, University Hospital, Ludwig-Maximilians-Universität München (LMU), Munich, GermanyWalter Brendel Centre of Experimental Medicine, University Hospital, Ludwig-Maximilians-Universität München (LMU) Munich, Munich, GermanyDepartment of Otorhinolaryngology, University Hospital, Ludwig-Maximilians-Universität München (LMU), Munich, GermanyWalter Brendel Centre of Experimental Medicine, University Hospital, Ludwig-Maximilians-Universität München (LMU) Munich, Munich, GermanyMicrovascular 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.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1078005/fullimmunothrombosisplateletsneutrophilsmicrovasculaturesystemic inflammationSIRS |
| spellingShingle | 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 Vitronectin promotes immunothrombotic dysregulation in the venular microvasculature Frontiers in Immunology immunothrombosis platelets neutrophils microvasculature systemic inflammation SIRS |
| title | Vitronectin promotes immunothrombotic dysregulation in the venular microvasculature |
| title_full | Vitronectin promotes immunothrombotic dysregulation in the venular microvasculature |
| title_fullStr | Vitronectin promotes immunothrombotic dysregulation in the venular microvasculature |
| title_full_unstemmed | Vitronectin promotes immunothrombotic dysregulation in the venular microvasculature |
| title_short | Vitronectin promotes immunothrombotic dysregulation in the venular microvasculature |
| title_sort | vitronectin promotes immunothrombotic dysregulation in the venular microvasculature |
| topic | immunothrombosis platelets neutrophils microvasculature systemic inflammation SIRS |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1078005/full |
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