Possible role of purinergic signaling in COVID-19

Franciosi, Maria Luiza Mukai; Lima, Millena Daher Medeiros; Schetinger, Maria Rosa Chitolina; Cardoso, Andréia Machado

doi:10.1007/s11010-021-04130-4

Cited by 34 publications

(34 citation statements)

References 54 publications

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“…iScience 24, 103478, December 17, 2021 iScience Article ATP and its metabolites have become a critical component of multiple diseases, including HIV and COVID-19 (Abouelkhair, 2020;Alves et al, 2020;de Oliveira et al, 2021;Dos Anjos et al, 2020;Edwards, 2021;Fonteles et al, 2020;Franciosi et al, 2021;Klaver and Thurnher, 2021;Mishra et al, 2021;Pacheco and Faria, 2021;Shan et al, 2020;Simoes and Bagatini, 2021). Our data in long-term HIV-infected individuals indicate that several chronic effects of HIV are correlated with ATP dysfunction and vascular disease, such as cognitive impairment (Velasquez et al, 2020).…”

Section: Ll Open Accessmentioning

confidence: 72%

Pannexin-1 channel opening is critical for COVID-19 pathogenesis

Luu¹,

Valdebenito²,

Scemes³

et al. 2021

iScience

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapidly rampaged worldwide, causing a pandemic of coronavirus disease (COVID -19), but the biology of SARS-CoV-2 remains under investigation. We demonstrate that both SARS-CoV-2 spike protein and human coronavirus 229E (hCoV-229E) or its purified S protein, one of the main viruses responsible for the common cold, induce the transient opening of Pannexin-1 (Panx-1) channels in human lung epithelial cells. However, the Panx-1 channel opening induced by SARS-CoV-2 is greater and more prolonged than hCoV-229E/S protein, resulting in an enhanced ATP, PGE 2 , and IL-1b release. Analysis of lung lavages and tissues indicate that Panx-1 mRNA expression is associated with increased ATP, PGE 2 , and IL-1b levels. Panx-1 channel opening induced by SARS-CoV-2 spike protein is angiotensin-converting enzyme 2 (ACE-2), endocytosis, and furin dependent. Overall, we demonstrated that Panx-1 channel is a critical contributor to SARS-CoV-2 infection and should be considered as an alternative therapy.

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Section: Ll Open Accessmentioning

confidence: 72%

Pannexin-1 channel opening is critical for COVID-19 pathogenesis

Luu¹,

Valdebenito²,

Scemes³

et al. 2021

iScience

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“…To date, the P2X7 receptor has been shown to be a strong activator of the NLRP3 inflammasome and therefore of caspase-1 cleavage and release of mature IL-1β and IL-18 [87]. In addition, the notable involvement of the inflammasome in COVID-19 has been recently discussed in multiple reports [24,87,[92][93][94][95][96].…”

Section: Purinergic Profile Of Circulating Immune Cellsmentioning

confidence: 99%

Purinergic signaling elements are correlated with coagulation players in peripheral blood and leukocyte samples from COVID-19 patients

2022

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For over a year, the coronavirus disease 2019 has been affecting the world population by causing severe tissue injuries and death in infected people. Adenosine triphosphate (ATP) and the nicotinamide adenine dinucleotide (NAD +) are two molecules that are released into the extracellular microenvironment after direct virus infection or cell death caused by hyper inflammation and coagulopathy. Also, these molecules are well known to participate in multiple pathways and have a pivotal role in the purinergic signaling pathway. Thus, using public datasets available on the Gene Expression Omnibus (GEO), we analyzed raw proteomics data acquired using mass spectrometry (the gold standard method) and raw genomics data from COVID-19 patient samples obtained by microarray. The data was analyzed using bioinformatics and statistical methods according to our objectives. Here, we compared the purinergic profile of the total leukocyte population and evaluated the levels of these soluble biomolecules in the blood, and their correlation with coagulation components in COVID-19 patients, in comparison to healthy people or non-COVID-19 patients. The blood metabolite analysis showed a stage-dependent inosine increase in COVID-19 patients, while the nucleotides ATP and ADP had positive correlations with fibrinogen and other coagulation proteins. Also, ATP, ADP, inosine, and hypoxanthine had positive and negative correlations with clinical features. Regarding leukocyte gene expression, COVID-19 patients showed an upregulation of the P2RX1, P2RX4, P2RX5, P2RX7, P2RY1, P2RY12, PANX1, ADORA2B, NLPR3, and F3 genes. Yet, the ectoenzymes of the canonical and non-canonical adenosinergic pathway (ENTPD1 and CD38) are upregulated, suggesting that adenosine is produced by both active adenosinergic pathways. Hence, approaches targeting these biomolecules or their specific purinoreceptors and ectoenzymes may attenuate the high inflammatory state and the coagulopathy seen in COVID-19 patients.

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“…Furthermore, CD39 is well described as a principal modulatory player in inflammation and coagulation (9,10) and its soluble form has been previously proposed as a prognosis biomarker in chronic obstructive pulmonary disease (11). Interestingly, a recent review by Franciosi et al (12), highlights the need for investigation about the prognostic value of CD39 levels in COVID-19 patients.…”

Section: Introductionmentioning

confidence: 99%

Role of CD39 in COVID-19 Severity: Dysregulation of Purinergic Signaling and Thromboinflammation

et al. 2022

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CD39/NTPDase1 has emerged as an important molecule that contributes to maintain inflammatory and coagulatory homeostasis. Various studies have hypothesized the possible role of CD39 in COVID-19 pathophysiology since no confirmatory data shed light in this regard. Therefore, we aimed to quantify CD39 expression on COVID-19 patients exploring its association with severity clinical parameters and ICU admission, while unraveling the role of purinergic signaling on thromboinflammation in COVID-19 patients. We selected a prospective cohort of patients hospitalized due to severe COVID-19 pneumonia (n=75), a historical cohort of Influenza A pneumonia patients (n=18) and sex/age-matched healthy controls (n=30). CD39 was overexpressed in COVID-19 patients’ plasma and immune cell subsets and related to hypoxemia. Plasma soluble form of CD39 (sCD39) was related to length of hospital stay and independently associated with intensive care unit admission (adjusted odds ratio 1.04, 95%CI 1.0-1.08, p=0.038), with a net reclassification index of 0.229 (0.118-0.287; p=0.036). COVID-19 patients showed extracellular accumulation of adenosine nucleotides (ATP and ADP), resulting in systemic inflammation and pro-coagulant state, as a consequence of purinergic pathway dysregulation. Interestingly, we found that COVID-19 plasma caused platelet activation, which was successfully blocked by the P2Y12 receptor inhibitor, ticagrelor. Therefore, sCD39 is suggested as a promising biomarker for COVID-19 severity. As a conclusion, our study indicates that CD39 overexpression in COVID-19 patients could be indicating purinergic signaling dysregulation, which might be at the basis of COVID-19 thromboinflammation disorder.

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Possible role of purinergic signaling in COVID-19

Cited by 34 publications

References 54 publications

Pannexin-1 channel opening is critical for COVID-19 pathogenesis

Pannexin-1 channel opening is critical for COVID-19 pathogenesis

Purinergic signaling elements are correlated with coagulation players in peripheral blood and leukocyte samples from COVID-19 patients

Role of CD39 in COVID-19 Severity: Dysregulation of Purinergic Signaling and Thromboinflammation

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