TY - JOUR
T1 - Alpha 1-acid glycoprotein is upregulated in severe COVID-19 patients and decreases neutrophil NETs in SARS-CoV-2 infection
AU - Mestriner, Fabiola
AU - Francisco, Daniely F.
AU - Campos, Ligia C.B.
AU - Couto, Ariel E.S.
AU - Fraga-Silva, Thais F.C.
AU - Flora Dugaich, Vinicius
AU - D Avila-Mesquita, Carolina
AU - Zukowski Kovacs, Henrique
AU - Vasconcelos, Jociany L.
AU - Milani, Elizabete R.
AU - Santos Guedes de Sá, Keyla
AU - Martins, Ronaldo
AU - Jordani, Maria C.
AU - Corsi, Carlos A.C.
AU - Barbosa, Jessyca M.
AU - Vasconcelos, Tauana
AU - Gonçalves Menegueti, Mayra
AU - Neto, Julio
AU - da Costa, Rafael M.
AU - Evora, Paulo R.B.
AU - Arruda, Eurico
AU - Tostes, Rita
AU - Polonis, Katarzyna
AU - Bonato, Vania L.D.
AU - Auxiliadora-Martins, Maria
AU - Ribeiro, Mauricio S.
AU - Becari, Christiane
N1 - Publisher Copyright:
© 2024 Elsevier Ltd
PY - 2024/4
Y1 - 2024/4
N2 - Orosomucoid, or alpha-1 acid glycoprotein (AGP), is a major acute-phase protein expressed in response to systemic injury and inflammation. AGP has been described as an inhibitor of neutrophil migration on sepsis, particularly its immunomodulation effects. AGP's biological functions in coronavirus disease 2019 (COVID-19) are not understood. We sought to investigate the role of AGP in severe COVID-19 infection patients and neutrophils infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Epidemiological data, AGP levels, and other laboratory parameters were measured in blood samples from 56 subjects hospitalized in the ICU with SARS-CoV-2 infection. To evaluate the role of AGP in NETosis in neutrophils, blood samples from health patients were collected, and neutrophils were separated and infected with SARS-CoV-2. Those neutrophils were treated with AGP or vehicle, and NETosis was analyzed by flow cytometry. AGP was upregulated in severe COVID-19 patients (p<0.05). AGP level was positively correlated with IL-6 and C-reactive protein (respectively, p=0.005, p=0.002) and negatively correlated with lactate (p=0.004). AGP treatment downregulated early and late NETosis (respectively, 35.7% and 43.5%) in neutrophils infected with SARS-CoV-2 and up-regulated IL-6 supernatant culture expression (p<0.0001). Our data showed increased AGP in COVID-19 infection and contributed to NETosis regulation and increased IL-6 production, possibly related to the Cytokine storm in COVID-19.
AB - Orosomucoid, or alpha-1 acid glycoprotein (AGP), is a major acute-phase protein expressed in response to systemic injury and inflammation. AGP has been described as an inhibitor of neutrophil migration on sepsis, particularly its immunomodulation effects. AGP's biological functions in coronavirus disease 2019 (COVID-19) are not understood. We sought to investigate the role of AGP in severe COVID-19 infection patients and neutrophils infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Epidemiological data, AGP levels, and other laboratory parameters were measured in blood samples from 56 subjects hospitalized in the ICU with SARS-CoV-2 infection. To evaluate the role of AGP in NETosis in neutrophils, blood samples from health patients were collected, and neutrophils were separated and infected with SARS-CoV-2. Those neutrophils were treated with AGP or vehicle, and NETosis was analyzed by flow cytometry. AGP was upregulated in severe COVID-19 patients (p<0.05). AGP level was positively correlated with IL-6 and C-reactive protein (respectively, p=0.005, p=0.002) and negatively correlated with lactate (p=0.004). AGP treatment downregulated early and late NETosis (respectively, 35.7% and 43.5%) in neutrophils infected with SARS-CoV-2 and up-regulated IL-6 supernatant culture expression (p<0.0001). Our data showed increased AGP in COVID-19 infection and contributed to NETosis regulation and increased IL-6 production, possibly related to the Cytokine storm in COVID-19.
KW - Alpha-1 acid glycoprotein (AGP)
KW - COVID-19 pathophysiology
KW - NETosis
KW - SARS-CoV-2 infection
UR - http://www.scopus.com/inward/record.url?scp=85183977103&partnerID=8YFLogxK
U2 - 10.1016/j.cyto.2024.156503
DO - 10.1016/j.cyto.2024.156503
M3 - Article
C2 - 38301358
AN - SCOPUS:85183977103
SN - 1043-4666
VL - 176
JO - Cytokine
JF - Cytokine
M1 - 156503
ER -