Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Sacchi, Alessandra, Grassi, Germana, Notari, Stefania, Gili, Simona, Bordoni, Veronica, Tartaglia, Eleonora, Casetti, Rita, Cimini, Eleonora, Mariotti, Davide, Garotto, Gabriele, Beccacece, Alessia, Marchioni, Luisa, Bibas, Michele, Nicastri, Emanuele, Ippolito, Giuseppe, Agrati, Chiara
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8391818/
https://www.ncbi.nlm.nih.gov/pubmed/34440879
http://dx.doi.org/10.3390/cells10082111
_version_ 1783743361319960576
author Sacchi, Alessandra
Grassi, Germana
Notari, Stefania
Gili, Simona
Bordoni, Veronica
Tartaglia, Eleonora
Casetti, Rita
Cimini, Eleonora
Mariotti, Davide
Garotto, Gabriele
Beccacece, Alessia
Marchioni, Luisa
Bibas, Michele
Nicastri, Emanuele
Ippolito, Giuseppe
Agrati, Chiara
author_facet Sacchi, Alessandra
Grassi, Germana
Notari, Stefania
Gili, Simona
Bordoni, Veronica
Tartaglia, Eleonora
Casetti, Rita
Cimini, Eleonora
Mariotti, Davide
Garotto, Gabriele
Beccacece, Alessia
Marchioni, Luisa
Bibas, Michele
Nicastri, Emanuele
Ippolito, Giuseppe
Agrati, Chiara
author_sort Sacchi, Alessandra
collection PubMed
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.
format Online
Article
Text
id pubmed-8391818
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-83918182021-08-28 Expansion of Myeloid Derived Suppressor Cells Contributes to Platelet Activation by L-Arginine Deprivation during SARS-CoV-2 Infection Sacchi, Alessandra Grassi, Germana Notari, Stefania Gili, Simona Bordoni, Veronica Tartaglia, Eleonora Casetti, Rita Cimini, Eleonora Mariotti, Davide Garotto, Gabriele Beccacece, Alessia Marchioni, Luisa Bibas, Michele Nicastri, Emanuele Ippolito, Giuseppe Agrati, Chiara Cells Brief Report 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. MDPI 2021-08-17 /pmc/articles/PMC8391818/ /pubmed/34440879 http://dx.doi.org/10.3390/cells10082111 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Brief Report
Sacchi, Alessandra
Grassi, Germana
Notari, Stefania
Gili, Simona
Bordoni, Veronica
Tartaglia, Eleonora
Casetti, Rita
Cimini, Eleonora
Mariotti, Davide
Garotto, Gabriele
Beccacece, Alessia
Marchioni, Luisa
Bibas, Michele
Nicastri, Emanuele
Ippolito, Giuseppe
Agrati, Chiara
Expansion of Myeloid Derived Suppressor Cells Contributes to Platelet Activation by L-Arginine Deprivation during SARS-CoV-2 Infection
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 Brief Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8391818/
https://www.ncbi.nlm.nih.gov/pubmed/34440879
http://dx.doi.org/10.3390/cells10082111
work_keys_str_mv AT sacchialessandra expansionofmyeloidderivedsuppressorcellscontributestoplateletactivationbylargininedeprivationduringsarscov2infection
AT grassigermana expansionofmyeloidderivedsuppressorcellscontributestoplateletactivationbylargininedeprivationduringsarscov2infection
AT notaristefania expansionofmyeloidderivedsuppressorcellscontributestoplateletactivationbylargininedeprivationduringsarscov2infection
AT gilisimona expansionofmyeloidderivedsuppressorcellscontributestoplateletactivationbylargininedeprivationduringsarscov2infection
AT bordoniveronica expansionofmyeloidderivedsuppressorcellscontributestoplateletactivationbylargininedeprivationduringsarscov2infection
AT tartagliaeleonora expansionofmyeloidderivedsuppressorcellscontributestoplateletactivationbylargininedeprivationduringsarscov2infection
AT casettirita expansionofmyeloidderivedsuppressorcellscontributestoplateletactivationbylargininedeprivationduringsarscov2infection
AT ciminieleonora expansionofmyeloidderivedsuppressorcellscontributestoplateletactivationbylargininedeprivationduringsarscov2infection
AT mariottidavide expansionofmyeloidderivedsuppressorcellscontributestoplateletactivationbylargininedeprivationduringsarscov2infection
AT garottogabriele expansionofmyeloidderivedsuppressorcellscontributestoplateletactivationbylargininedeprivationduringsarscov2infection
AT beccacecealessia expansionofmyeloidderivedsuppressorcellscontributestoplateletactivationbylargininedeprivationduringsarscov2infection
AT marchioniluisa expansionofmyeloidderivedsuppressorcellscontributestoplateletactivationbylargininedeprivationduringsarscov2infection
AT bibasmichele expansionofmyeloidderivedsuppressorcellscontributestoplateletactivationbylargininedeprivationduringsarscov2infection
AT nicastriemanuele expansionofmyeloidderivedsuppressorcellscontributestoplateletactivationbylargininedeprivationduringsarscov2infection
AT ippolitogiuseppe expansionofmyeloidderivedsuppressorcellscontributestoplateletactivationbylargininedeprivationduringsarscov2infection
AT agratichiara expansionofmyeloidderivedsuppressorcellscontributestoplateletactivationbylargininedeprivationduringsarscov2infection