Expansion of Myeloid Derived Suppressor Cells Contributes to Platelet Activation by L-Arginine Deprivation during SARS-CoV-2 Infection

Massive platelet activation and thrombotic events characterize severe COVID-19, highlighting their critical role in SARS-CoV-2-induced immunopathology. Since there is a well-described expansion of myeloid-derived suppressor cells (MDSC) in severe COVID-19, we evaluated their possible role in platele...

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Main Authors: Alessandra Sacchi, Germana Grassi, Stefania Notari, Simona Gili, Veronica Bordoni, Eleonora Tartaglia, Rita Casetti, Eleonora Cimini, Davide Mariotti, Gabriele Garotto, Alessia Beccacece, Luisa Marchioni, Michele Bibas, Emanuele Nicastri, Giuseppe Ippolito, Chiara Agrati
Format: Article
Language:English
Published: MDPI AG 2021-08-01
Series:Cells
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Online Access:https://www.mdpi.com/2073-4409/10/8/2111
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author Alessandra Sacchi
Germana Grassi
Stefania Notari
Simona Gili
Veronica Bordoni
Eleonora Tartaglia
Rita Casetti
Eleonora Cimini
Davide Mariotti
Gabriele Garotto
Alessia Beccacece
Luisa Marchioni
Michele Bibas
Emanuele Nicastri
Giuseppe Ippolito
Chiara Agrati
author_facet Alessandra Sacchi
Germana Grassi
Stefania Notari
Simona Gili
Veronica Bordoni
Eleonora Tartaglia
Rita Casetti
Eleonora Cimini
Davide Mariotti
Gabriele Garotto
Alessia Beccacece
Luisa Marchioni
Michele Bibas
Emanuele Nicastri
Giuseppe Ippolito
Chiara Agrati
author_sort Alessandra Sacchi
collection DOAJ
description Massive platelet activation and thrombotic events characterize severe COVID-19, highlighting their critical role in SARS-CoV-2-induced immunopathology. Since there is a well-described expansion of myeloid-derived suppressor cells (MDSC) in severe COVID-19, we evaluated their possible role in platelet activation during SARS-CoV-2 infection. During COVID-19, a lower plasmatic L-arginine level was observed compared to healthy donors, which correlated with MDSC frequency. Additionally, activated GPIIb/IIIa complex (PAC-1) expression was higher on platelets from severe COVID-19 patients compared to healthy controls and inversely correlated with L-arginine plasmatic concentration. Notably, MDSC were able to induce PAC-1 expression in vitro by reducing L-arginine concentration, indicating a direct role of PMN-MDSC in platelet activation. Accordingly, we found a positive correlation between ex vivo platelet PAC-1 expression and PMN-MDSC frequency. Overall, our data demonstrate the involvement of PMN-MDSC in triggering platelet activation during COVID-19, highlighting a novel role of MDSC in driving COVID-19 pathogenesis.
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spelling doaj.art-218f0a080f1b402ea189986c938540942023-11-22T07:11:53ZengMDPI AGCells2073-44092021-08-01108211110.3390/cells10082111Expansion of Myeloid Derived Suppressor Cells Contributes to Platelet Activation by L-Arginine Deprivation during SARS-CoV-2 InfectionAlessandra Sacchi0Germana Grassi1Stefania Notari2Simona Gili3Veronica Bordoni4Eleonora Tartaglia5Rita Casetti6Eleonora Cimini7Davide Mariotti8Gabriele Garotto9Alessia Beccacece10Luisa Marchioni11Michele Bibas12Emanuele Nicastri13Giuseppe Ippolito14Chiara Agrati15Department of Epidemiology, Pre-Clinical Research and Advanced Diagnostic, National Institute for Infectious Diseases “Lazzaro Spallanzani”-IRCCS, Via Portuense, 292-00149 Rome, ItalyDepartment of Epidemiology, Pre-Clinical Research and Advanced Diagnostic, National Institute for Infectious Diseases “Lazzaro Spallanzani”-IRCCS, Via Portuense, 292-00149 Rome, ItalyDepartment of Epidemiology, Pre-Clinical Research and Advanced Diagnostic, National Institute for Infectious Diseases “Lazzaro Spallanzani”-IRCCS, Via Portuense, 292-00149 Rome, ItalyDepartment of Epidemiology, Pre-Clinical Research and Advanced Diagnostic, National Institute for Infectious Diseases “Lazzaro Spallanzani”-IRCCS, Via Portuense, 292-00149 Rome, ItalyDepartment of Epidemiology, Pre-Clinical Research and Advanced Diagnostic, National Institute for Infectious Diseases “Lazzaro Spallanzani”-IRCCS, Via Portuense, 292-00149 Rome, ItalyDepartment of Epidemiology, Pre-Clinical Research and Advanced Diagnostic, National Institute for Infectious Diseases “Lazzaro Spallanzani”-IRCCS, Via Portuense, 292-00149 Rome, ItalyDepartment of Epidemiology, Pre-Clinical Research and Advanced Diagnostic, National Institute for Infectious Diseases “Lazzaro Spallanzani”-IRCCS, Via Portuense, 292-00149 Rome, ItalyDepartment of Epidemiology, Pre-Clinical Research and Advanced Diagnostic, National Institute for Infectious Diseases “Lazzaro Spallanzani”-IRCCS, Via Portuense, 292-00149 Rome, ItalyDepartment of Epidemiology, Pre-Clinical Research and Advanced Diagnostic, National Institute for Infectious Diseases “Lazzaro Spallanzani”-IRCCS, Via Portuense, 292-00149 Rome, ItalyClinical Department, National Institute for Infectious Diseases “Lazzaro Spallanzani”-IRCCS, Via Portuense, 292-00149 Rome, ItalyClinical Department, National Institute for Infectious Diseases “Lazzaro Spallanzani”-IRCCS, Via Portuense, 292-00149 Rome, ItalyClinical Department, National Institute for Infectious Diseases “Lazzaro Spallanzani”-IRCCS, Via Portuense, 292-00149 Rome, ItalyClinical Department, National Institute for Infectious Diseases “Lazzaro Spallanzani”-IRCCS, Via Portuense, 292-00149 Rome, ItalyClinical Department, National Institute for Infectious Diseases “Lazzaro Spallanzani”-IRCCS, Via Portuense, 292-00149 Rome, ItalyNational Institute for Infectious Diseases “Lazzaro Spallanzani”-IRCCS, Via Portuense, 292-00149 Rome, ItalyDepartment of Epidemiology, Pre-Clinical Research and Advanced Diagnostic, National Institute for Infectious Diseases “Lazzaro Spallanzani”-IRCCS, Via Portuense, 292-00149 Rome, ItalyMassive platelet activation and thrombotic events characterize severe COVID-19, highlighting their critical role in SARS-CoV-2-induced immunopathology. Since there is a well-described expansion of myeloid-derived suppressor cells (MDSC) in severe COVID-19, we evaluated their possible role in platelet activation during SARS-CoV-2 infection. During COVID-19, a lower plasmatic L-arginine level was observed compared to healthy donors, which correlated with MDSC frequency. Additionally, activated GPIIb/IIIa complex (PAC-1) expression was higher on platelets from severe COVID-19 patients compared to healthy controls and inversely correlated with L-arginine plasmatic concentration. Notably, MDSC were able to induce PAC-1 expression in vitro by reducing L-arginine concentration, indicating a direct role of PMN-MDSC in platelet activation. Accordingly, we found a positive correlation between ex vivo platelet PAC-1 expression and PMN-MDSC frequency. Overall, our data demonstrate the involvement of PMN-MDSC in triggering platelet activation during COVID-19, highlighting a novel role of MDSC in driving COVID-19 pathogenesis.https://www.mdpi.com/2073-4409/10/8/2111COVID-19MDSCplateletL-Arginine
spellingShingle Alessandra Sacchi
Germana Grassi
Stefania Notari
Simona Gili
Veronica Bordoni
Eleonora Tartaglia
Rita Casetti
Eleonora Cimini
Davide Mariotti
Gabriele Garotto
Alessia Beccacece
Luisa Marchioni
Michele Bibas
Emanuele Nicastri
Giuseppe Ippolito
Chiara Agrati
Expansion of Myeloid Derived Suppressor Cells Contributes to Platelet Activation by L-Arginine Deprivation during SARS-CoV-2 Infection
Cells
COVID-19
MDSC
platelet
L-Arginine
title Expansion of Myeloid Derived Suppressor Cells Contributes to Platelet Activation by L-Arginine Deprivation during SARS-CoV-2 Infection
title_full Expansion of Myeloid Derived Suppressor Cells Contributes to Platelet Activation by L-Arginine Deprivation during SARS-CoV-2 Infection
title_fullStr Expansion of Myeloid Derived Suppressor Cells Contributes to Platelet Activation by L-Arginine Deprivation during SARS-CoV-2 Infection
title_full_unstemmed Expansion of Myeloid Derived Suppressor Cells Contributes to Platelet Activation by L-Arginine Deprivation during SARS-CoV-2 Infection
title_short Expansion of Myeloid Derived Suppressor Cells Contributes to Platelet Activation by L-Arginine Deprivation during SARS-CoV-2 Infection
title_sort expansion of myeloid derived suppressor cells contributes to platelet activation by l arginine deprivation during sars cov 2 infection
topic COVID-19
MDSC
platelet
L-Arginine
url https://www.mdpi.com/2073-4409/10/8/2111
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