The role of the P2X7 receptor in inactivated SARS-CoV-2-induced lung injury

被引：1

作者：

Carvalho-Barbosa, N. C. ^{[1
]}

Cristina-Rodrigues, Fabiana ^{[1
]}

Temerozo, Jairo R. ^{[2
,3
]}

Souza, Thiago M. L. ^{[4
,5
]}

Gouvea, Andre L. ^{[6
]}

Canetti, Claudio A. ^{[7
]}

Kurtenbach, Eleonora ^{[6
]}

Bou-Habib, Dumith Chequer ^{[2
,3
]}

Benjamim, Claudia F. ^{[8
]}

Takiya, Christina M. ^{[9
]}

Savio, Luiz E. B. ^{[1
]}

Coutinho-Silva, Robson ^{[1
]}

机构：

[1] Univ Fed Rio de Janeiro, Inst Biophys Carlos Chagas Filho, Lab Immunophysiol, Rio De Janeiro, RJ, Brazil

[2] Oswaldo Cruz Inst Fiocruz, Lab Thymus Res, Rio De Janeiro, RJ, Brazil

[3] Natl Inst Sci & Technol Neuroimmunomodulat, Rio De Janeiro, Brazil

[4] Oswaldo Cruz Inst Fiocruz, Lab Immunopharmacol, Rio De Janeiro, Brazil

[5] Fiocruz MS, Natl Inst Sci & Technol Innovat Dis Neglected Popu, Ctr Technol Dev Hlth, Rio De Janeiro, Brazil

[6] Univ Fed Rio de Janeiro, Inst Biophys Carlos Chagas Filho, Lab Prot Biochem, Rio De Janeiro, RJ, Brazil

[7] Univ Fed Rio de Janeiro, Inst Biophys Carlos Chagas Filho, Lab Inflammat, Rio De Janeiro, RJ, Brazil

[8] Univ Fed Rio de Janeiro, Inst Biophys Carlos Chagas Filho, Lab Mol & Cellular Immunol, Rio De Janeiro, RJ, Brazil

[9] Univ Fed Rio de Janeiro, Inst Biophys Carlos Chagas Filho, Lab Immunopathol, Rio De Janeiro, RJ, Brazil

来源：

PURINERGIC SIGNALLING | 2025年 / 21卷 / 03期

关键词：

Purinergic signaling; P2Y(12); ATP; CD39; Lung inflammation; COVID-19; EXTRACELLULAR ATP; ADENOSINE-TRIPHOSPHATE; P2Y(12); INFLAMMATION; RELEASE; VIRUS; CELLS; IDENTIFICATION; ACTIVATION; INFECTION;

D O I：

10.1007/s11302-024-10062-7

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Purinergic signaling plays a role in the pathophysiology of different viral infections. Recently, we showed that COVID-19 increases extracellular ATP levels, which may amplify the pro-inflammatory signals in the disease. The P2X7 receptor can be a protagonist in the pro-inflammatory responses. Herein, we investigated the role of the P2X7 receptor in the lung immune response triggered by inoculation of inactivated SARS-CoV-2 (iSARS-CoV-2) in K18-Human ACE2 transgenic mice. Pharmacological inhibition of the P2X7 receptor was performed with intraperitoneal administration of 50 mg/kg of Brilliant Blue G (BBG) one day before viral inoculation. Animals were divided into four groups: a control group (MOCK), a group inoculated with the inactivated virus iSARS-CoV-2, a BBG-treated control group (MOCK + BBG), and a BBG-treated inoculated group (iSARS-CoV-2 + BBG). Virus inoculation was intratracheal with 50 mu l of mock or 2 x 10(6) Plaque Forming Units (PFU) of iSARS-CoV-2. After three days, blood and lungs were collected. We found a significant increase in ATP and LDH in serum and mRNA levels of P2X7 and P2Y(12) receptors, CD39, IL-1 beta, and TNF-alpha in the lung of the iSARS-CoV-2 group when compared with the control group. BBG treatment attenuated these increases. Lung histological analyses showed severe lung damage in the iSARS-CoV-2 group, which was reduced by the BBG treatment. Immunohistochemical staining confirmed the increased presence of P2X7, P2Y(12), and CD39 proteins in the iSARS-CoV-2 vs. the MOCK group. Thus, P2X7 receptor inhibition decreases iSARS-CoV-2-induced lung inflammation, indicating that this receptor might contribute to SARS-CoV-2 pathology.

引用

页码：465 / 483

页数：19

共 77 条

[21] A rationale for targeting the P2X7 receptor in Coronavirus disease 19 [J].