Vitronectin promotes immunothrombotic dysregulation in the venular microvasculature

Bernd Uhl; Florian Haring; Julia Slotta-Huspenina; Joshua Luft; Vera Schneewind; Jonas Hildinger; Zhengquan Wu; Katja Steiger; Bojan Smiljanov; Aarif M.N. Batcha; Oliver T. Keppler; Johannes C. Hellmuth; Tobias Lahmer; Konrad Stock; Bernhard G. Weiss; Martin Canis; Konstantin Stark; Thomas Bromberger; Markus Moser; Christian Schulz; Wilko Weichert; Gabriele Zuchtriegel; Christoph A. Reichel

doi:10.3389/fimmu.2023.1078005

Vitronectin promotes immunothrombotic dysregulation in the venular microvasculature

Bernd Uhl, Florian Haring, Julia Slotta-Huspenina, Joshua Luft, Vera Schneewind, Jonas Hildinger, Zhengquan Wu, Katja Steiger, Bojan Smiljanov, Aarif M.N. Batcha, Oliver T. Keppler, Johannes C. Hellmuth, Tobias Lahmer, Konrad Stock, Bernhard G. Weiss, Martin Canis, Konstantin Stark, Thomas Bromberger, Markus Moser, Christian SchulzWilko Weichert, Gabriele Zuchtriegel, Christoph A. Reichel

Research output: Contribution to journal › Article › peer-review

1 Scopus citations

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.

Original language	English
Article number	1078005
Journal	Frontiers in Immunology
Volume	14
DOIs	https://doi.org/10.3389/fimmu.2023.1078005
State	Published - 8 Feb 2023

Keywords

SIRS
immunothrombosis
microvasculature
neutrophils
platelets
systemic inflammation
vitronectin

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10.3389/fimmu.2023.1078005

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Uhl, B., Haring, F., Slotta-Huspenina, J., Luft, J., Schneewind, V., Hildinger, J., Wu, Z., Steiger, K., Smiljanov, B., Batcha, A. M. N., Keppler, O. T., Hellmuth, J. C., Lahmer, T., Stock, K., Weiss, B. G., Canis, M., Stark, K., Bromberger, T., Moser, M., ... Reichel, C. A. (2023). Vitronectin promotes immunothrombotic dysregulation in the venular microvasculature. Frontiers in Immunology, 14, Article 1078005. https://doi.org/10.3389/fimmu.2023.1078005

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title = "Vitronectin promotes immunothrombotic dysregulation in the venular microvasculature",

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",

author = "Bernd Uhl and Florian Haring and Julia Slotta-Huspenina and Joshua Luft and Vera Schneewind and Jonas Hildinger and Zhengquan Wu and Katja Steiger and Bojan Smiljanov and Batcha, {Aarif M.N.} and Keppler, {Oliver T.} and Hellmuth, {Johannes C.} and Tobias Lahmer and Konrad Stock and Weiss, {Bernhard G.} and Martin Canis and Konstantin Stark and Thomas Bromberger and Markus Moser and Christian Schulz and Wilko Weichert and Gabriele Zuchtriegel and Reichel, {Christoph A.}",

note = "Publisher Copyright: Copyright {\textcopyright} 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.",

year = "2023",

month = feb,

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doi = "10.3389/fimmu.2023.1078005",

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Uhl, B, Haring, F, Slotta-Huspenina, J, Luft, J, Schneewind, V, Hildinger, J, Wu, Z, Steiger, K, Smiljanov, B, Batcha, AMN, Keppler, OT, Hellmuth, JC, Lahmer, T, Stock, K, Weiss, BG, Canis, M, Stark, K, Bromberger, T, Moser, M, Schulz, C, Weichert, W, Zuchtriegel, G & Reichel, CA 2023, 'Vitronectin promotes immunothrombotic dysregulation in the venular microvasculature', Frontiers in Immunology, vol. 14, 1078005. https://doi.org/10.3389/fimmu.2023.1078005

TY - JOUR

T1 - Vitronectin promotes immunothrombotic dysregulation in the venular microvasculature

AU - Uhl, Bernd

AU - Haring, Florian

AU - Slotta-Huspenina, Julia

AU - Luft, Joshua

AU - Schneewind, Vera

AU - Hildinger, Jonas

AU - Wu, Zhengquan

AU - Steiger, Katja

AU - Smiljanov, Bojan

AU - Batcha, Aarif M.N.

AU - Keppler, Oliver T.

AU - Hellmuth, Johannes C.

AU - Lahmer, Tobias

AU - Stock, Konrad

AU - Weiss, Bernhard G.

AU - Canis, Martin

AU - Stark, Konstantin

AU - Bromberger, Thomas

AU - Moser, Markus

AU - Schulz, Christian

AU - Weichert, Wilko

AU - Zuchtriegel, Gabriele

AU - Reichel, Christoph A.

N1 - Publisher Copyright: 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.

PY - 2023/2/8

Y1 - 2023/2/8

N2 - 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.

AB - 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.

KW - SIRS

KW - immunothrombosis

KW - microvasculature

KW - neutrophils

KW - platelets

KW - systemic inflammation

KW - vitronectin

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U2 - 10.3389/fimmu.2023.1078005

DO - 10.3389/fimmu.2023.1078005

M3 - Article

AN - SCOPUS:85148640913

SN - 1664-3224

VL - 14

JO - Frontiers in Immunology

JF - Frontiers in Immunology

M1 - 1078005

ER -

Vitronectin promotes immunothrombotic dysregulation in the venular microvasculature

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Keywords

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