Dysfunctional purinergic signaling correlates with disease severity in COVID-19 patients

Ectonucleotidases modulate inflammatory responses by balancing extracellular ATP and adenosine (ADO) and might be involved in COVID-19 immunopathogenesis. Here, we explored the contribution of extracellular nucleotide metabolism to COVID-19 severity in mild and severe cases of the disease. We verified that the gene expression of ectonucleotidases is reduced in the whole blood of patients with COVID-19 and is negatively correlated to levels of CRP, an inflammatory marker of disease severity. In line with these findings, COVID-19 patients present higher ATP levels in plasma and reduced levels of ADO when compared to healthy controls. Cell type-specific analysis revealed higher frequencies of CD39+ T cells in severely ill patients, while CD4+ and CD8+ expressing CD73 are reduced in this same group. The frequency of B cells CD39+CD73+ is also decreased during acute COVID-19. Interestingly, B cells from COVID-19 patients showed a reduced capacity to hydrolyze ATP into ADP and ADO. Furthermore, impaired expression of ADO receptors and a compromised activation of its signaling pathway is observed in COVID-19 patients. The presence of ADO in vitro, however, suppressed inflammatory responses triggered in patients’ cells. In summary, our findings support the idea that alterations in the metabolism of extracellular purines contribute to immune dysregulation during COVID-19, possibly favoring disease severity, and suggest that ADO may be a therapeutic approach for the disease

Aerobic Exercise Reduces Asthma Phenotype by Modulation of the Leukotriene Pathway

Submitted by Sandra Infurna ([email protected]) on 2016-12-01T11:17:20Z No. of bitstreams: 1 hugo_farianeto_etal_IOC_2016.pdf: 2748450 bytes, checksum: 98a1c02d5f24481572e9101bed50a250 (MD5)Approved for entry into archive by Sandra Infurna ([email protected]) on 2016-12-01T11:42:37Z (GMT) No. of bitstreams: 1 hugo_farianeto_etal_IOC_2016.pdf: 2748450 bytes, checksum: 98a1c02d5f24481572e9101bed50a250 (MD5)Made available in DSpace on 2016-12-01T11:42:37Z (GMT). No. of bitstreams: 1 hugo_farianeto_etal_IOC_2016.pdf: 2748450 bytes, checksum: 98a1c02d5f24481572e9101bed50a250 (MD5) Previous issue date: 2016Nove de Julho University (UNINOVE). Brazilian Institute of Teaching and Research in Pulmonary and Exercise Immunology (IBEPIPE). Laboratory of Pulmonary and Exercise Immunology (LABPEI). São Paulo, SP, Brazil.Nove de Julho University (UNINOVE). Brazilian Institute of Teaching and Research in Pulmonary and Exercise Immunology (IBEPIPE). Laboratory of Pulmonary and Exercise Immunology (LABPEI). São Paulo, SP, Brazil.Nove de Julho University (UNINOVE). Brazilian Institute of Teaching and Research in Pulmonary and Exercise Immunology (IBEPIPE). Laboratory of Pulmonary and Exercise Immunology (LABPEI). São Paulo, SP, Brazil.Nove de Julho University (UNINOVE). Brazilian Institute of Teaching and Research in Pulmonary and Exercise Immunology (IBEPIPE). Laboratory of Pulmonary and Exercise Immunology (LABPEI). São Paulo, SP, Brazil.Nove de Julho University (UNINOVE). Brazilian Institute of Teaching and Research in Pulmonary and Exercise Immunology (IBEPIPE). Laboratory of Pulmonary and Exercise Immunology (LABPEI). São Paulo, SP, Brazil.Nove de Julho University (UNINOVE). Brazilian Institute of Teaching and Research in Pulmonary and Exercise Immunology (IBEPIPE). Laboratory of Pulmonary and Exercise Immunology (LABPEI). São Paulo, SP, Brazil.Nove de Julho University (UNINOVE). Brazilian Institute of Teaching and Research in Pulmonary and Exercise Immunology (IBEPIPE). Laboratory of Pulmonary and Exercise Immunology (LABPEI). São Paulo, SP, Brazil.University of São Paulo (USP). School of Medicine. Laboratory of Cellular Biology (LIM59). São Paulo, SP, Brazil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.University of São Paulo (USP). School of Medicine. Laboratory of Experimental Therapeutics (LIM 20). São Paulo, SP, Brazil.University of São Paulo (USP). School of Medicine. Laboratory of Experimental Therapeutics (LIM 20). São Paulo, SP, Brazil.University of California Irvine. Institute for Memory Impairments and Neurological Disorders (MIND Institute). Irvine, CA, USA.University of São Paulo (USP). School of Medicine. Department of Pathology (LIM 05). São Paulo, SP, Brazil.University Hospital Freiburg. Department of Pneumology. COPD and Asthma Research Group. Freiburg, Germany.Nove de Julho University (UNINOVE). Brazilian Institute of Teaching and Research in Pulmonary and Exercise Immunology (IBEPIPE). Laboratory of Pulmonary and Exercise Immunology (LABPEI). São Paulo, SP, Brazil.University of Tübingen. Department of Pneumology. Institute of Clinical and Experimental Transfusion Medicine (IKET). Tübingen, Germany.Nove de Julho University (UNINOVE). Brazilian Institute of Teaching and Research in Pulmonary and Exercise Immunology (IBEPIPE). Laboratory of Pulmonary and Exercise Immunology (LABPEI). São Paulo, SP, Brazil.Leukotrienes (LTs) play a central role in asthma. Low- to moderate-intensity aerobic exercise (AE) reduces asthmatic inflammation in clinical studies and in experimental models. This study investigated whether AE attenuates LT pathway activation in an ovalbumin (OVA) model of asthma