Growth Arrest-Specific Factor 6 (GAS6) Is Increased in COVID-19 Patients and Predicts Clinical Outcome.
AXL
COVID-19
GAS6
MERTK
immune response
immunothrombosis
viral infection
vitamin K
Journal
Biomedicines
ISSN: 2227-9059
Titre abrégé: Biomedicines
Pays: Switzerland
ID NLM: 101691304
Informations de publication
Date de publication:
26 Mar 2021
26 Mar 2021
Historique:
received:
12
03
2021
revised:
19
03
2021
accepted:
23
03
2021
entrez:
3
4
2021
pubmed:
4
4
2021
medline:
4
4
2021
Statut:
epublish
Résumé
Growth arrest-specific factor 6 (GAS6) and the Tyro3, AXL, and MERTK (TAM) receptors counterbalance pro-inflammatory responses. AXL is a candidate receptor for SARS-CoV-2, particularly in the respiratory system, and the GAS6/AXL axis is targeted in current clinical trials against COVID-19. However, GAS6 and TAMs have not been evaluated in COVID-19 patients at emergency admission. Plasma GAS6, AXL, and MERTK were analyzed in 132 patients consecutively admitted to the emergency ward during the first peak of COVID-19. GAS6 levels were higher in the SARS-CoV-2-positive patients, increasing progressively with the severity of the disease. Patients with initial GAS6 at the highest quartile had the worst outcome, with a 3-month survival of 65%, compared to a 90% survival for the rest. Soluble AXL exhibited higher plasma concentration in deceased patients, without significant differences in MERTK among SARS-CoV-2-positive groups. GAS6 mRNA was mainly expressed in alveolar cells and AXL in airway macrophages. Remarkably, THP-1 human macrophage differentiation neatly induces AXL, and its inhibition (bemcentinib) reduced cytokine production in human macrophages after LPS challenge. Plasma GAS6 and AXL levels reflect COVID-19 severity and could be early markers of disease prognosis, supporting a relevant role of the GAS6/AXL system in the immune response in COVID-19.
Sections du résumé
BACKGROUND
BACKGROUND
Growth arrest-specific factor 6 (GAS6) and the Tyro3, AXL, and MERTK (TAM) receptors counterbalance pro-inflammatory responses. AXL is a candidate receptor for SARS-CoV-2, particularly in the respiratory system, and the GAS6/AXL axis is targeted in current clinical trials against COVID-19. However, GAS6 and TAMs have not been evaluated in COVID-19 patients at emergency admission.
METHODS
METHODS
Plasma GAS6, AXL, and MERTK were analyzed in 132 patients consecutively admitted to the emergency ward during the first peak of COVID-19.
RESULTS
RESULTS
GAS6 levels were higher in the SARS-CoV-2-positive patients, increasing progressively with the severity of the disease. Patients with initial GAS6 at the highest quartile had the worst outcome, with a 3-month survival of 65%, compared to a 90% survival for the rest. Soluble AXL exhibited higher plasma concentration in deceased patients, without significant differences in MERTK among SARS-CoV-2-positive groups. GAS6 mRNA was mainly expressed in alveolar cells and AXL in airway macrophages. Remarkably, THP-1 human macrophage differentiation neatly induces AXL, and its inhibition (bemcentinib) reduced cytokine production in human macrophages after LPS challenge.
CONCLUSIONS
CONCLUSIONS
Plasma GAS6 and AXL levels reflect COVID-19 severity and could be early markers of disease prognosis, supporting a relevant role of the GAS6/AXL system in the immune response in COVID-19.
Identifiants
pubmed: 33810394
pii: biomedicines9040335
doi: 10.3390/biomedicines9040335
pmc: PMC8065652
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : Ministerio de Ciencia e Innovación
ID : RTI2018-095672-B-I00
Organisme : Instituto de Salud Carlos III
ID : PI15/00531, PI19/01410
Organisme : Fundació la Marató de TV3
ID : 20153030 and 20153031
Organisme : European Union
ID : ERDF "A way to make Europe"
Organisme : Consejo Superior de Investigaciones Científicas
ID : CSIC-COV19-016/202020E155
Organisme : Junta de Castilla y León
ID : 07.04.467B04.74011.0
Organisme : CERCA Programme/Generalitat de Catalunya
ID : AGAUR 2017_SGR_177
Références
Science. 2015 Jan 23;347(6220):1260419
pubmed: 25613900
Clin Chim Acta. 2020 Oct;509:280-287
pubmed: 32531256
Cell Res. 2021 Feb;31(2):126-140
pubmed: 33420426
Front Pharmacol. 2019 Jun 13;10:662
pubmed: 31263416
J Clin Invest. 2020 Jun 1;130(6):3021-3037
pubmed: 32364537
Cell Mol Gastroenterol Hepatol. 2020;9(3):349-368
pubmed: 31689560
Int J Cardiol. 2014 May 15;173(3):402-9
pubmed: 24681018
Mol Med. 2020 Oct 29;26(1):97
pubmed: 33121429
Tohoku J Exp Med. 2017;243(3):187-193
pubmed: 29176262
J Exp Med. 2019 Sep 2;216(9):2184-2201
pubmed: 31289116
Nutrients. 2020 Dec 24;13(1):
pubmed: 33374341
PLoS One. 2016 Oct 27;11(10):e0163542
pubmed: 27788141
Crit Care. 2007;11(1):R8
pubmed: 17241453
Dermatol Ther. 2020 Jul;33(4):e13681
pubmed: 32447798
Cell Rep. 2017 Jan 10;18(2):324-333
pubmed: 28076778
J Hepatol. 2015 Sep;63(3):670-8
pubmed: 25908269
Blood. 2008 Apr 15;111(8):4096-105
pubmed: 18156494
Vitam Horm. 2008;78:185-209
pubmed: 18374195
Cells. 2020 Sep 28;9(10):
pubmed: 32998369
Curr Nutr Rep. 2020 Sep;9(3):226-235
pubmed: 32602055
J Virol. 2011 Jan;85(1):334-47
pubmed: 21047970
J Allergy Clin Immunol. 2017 Oct;140(4):1144-1146.e4
pubmed: 28412392
Nephrol Dial Transplant. 2012 Nov;27(11):4166-72
pubmed: 22907951
Clin Infect Dis. 2020 Aug 27;:
pubmed: 32852539
Dis Markers. 2019 Aug 14;2019:6156493
pubmed: 31485279
Crit Care. 2010;14(4):R158
pubmed: 20731857
Crit Care Med. 2006 Jan;34(1):219-22
pubmed: 16374177
J Thorac Oncol. 2016 Aug;11(8):1357-1362
pubmed: 27130831
Pathogens. 2020 Jun 20;9(6):
pubmed: 32575786