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2. SARS-CoV-2 Spike Protein Activates Human Lung Macrophages

Author

Palestra, Francesco, primary, Poto, Remo, additional, Ciardi, Renato, additional, Opromolla, Giorgia, additional, Secondo, Agnese, additional, Tedeschi, Valentina, additional, Ferrara, Anne Lise, additional, Di Crescenzo, Rosa Maria, additional, Galdiero, Maria Rosaria, additional, Cristinziano, Leonardo, additional, Modestino, Luca, additional, Marone, Gianni, additional, Fiorelli, Alfonso, additional, Varricchi, Gilda, additional, and Loffredo, Stefania, additional

Published
2023
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3. Interplay between C1-inhibitor and group IIA secreted phospholipase A2 impairs their respective function

Author

Ferrara, Anne Lise, primary, Bova, Maria, additional, Petraroli, Angelica, additional, Marasco, Daniela, additional, Payré, Christine, additional, Fortuna, Sara, additional, Palestra, Francesco, additional, Ciardi, Renato, additional, Marone, Gianni, additional, Spadaro, Giuseppe, additional, Lambeau, Gérard, additional, and Loffredo, Stefania, additional

Published
2022
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4. Size-based effects of anthropogenic ultrafine particles on activation of human lung macrophages

Author

Marcella, Simone, primary, Apicella, Barbara, additional, Secondo, Agnese, additional, Palestra, Francesco, additional, Opromolla, Giorgia, additional, Ciardi, Renato, additional, Tedeschi, Valentina, additional, Ferrara, Anne Lise, additional, Russo, Carmela, additional, Rosaria Galdiero, Maria, additional, Cristinziano, Leonardo, additional, Modestino, Luca, additional, Spadaro, Giuseppe, additional, Fiorelli, Alfonso, additional, and Loffredo, Stefania, additional

Published
2022
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5. Interplay between C1-inhibitor and group IIA secreted phospholipase A2 impairs their respective function.

Author

Ferrara, Anne Lise, Bova, Maria, Petraroli, Angelica, Marasco, Daniela, Payré, Christine, Fortuna, Sara, Palestra, Francesco, Ciardi, Renato, Marone, Gianni, Spadaro, Giuseppe, Lambeau, Gérard, and Loffredo, Stefania

Abstract

High levels of human group IIA secreted phospholipase A2 (hGIIA) have been associated with various inflammatory disease conditions. We have recently shown that hGIIA activity and concentration are increased in the plasma of patients with hereditary angioedema due to C1-inhibitor deficiency (C1-INH-HAE) and negatively correlate with C1-INH plasma activity. In this study, we analyzed whether the presence of both hGIIA and C1-INH impairs their respective function on immune cells. hGIIA, but not recombinant and plasma-derived C1-INH, stimulates the production of IL-6, CXCL8, and TNF-α from peripheral blood mononuclear cells (PBMCs). PBMC activation mediated by hGIIA is blocked by RO032107A, a specific hGIIA inhibitor. Interestingly, C1-INH inhibits the hGIIA-induced production of IL-6, TNF-α, and CXCL8, while it does not affect hGIIA enzymatic activity. On the other hand, hGIIA reduces the capacity of C1-INH at inhibiting C1-esterase activity. Spectroscopic and molecular docking studies suggest a possible interaction between hGIIA and C1-INH but further experiments are needed to confirm this hypothesis. Together, these results provide evidence for a new interplay between hGIIA and C1-INH, which may be important in the pathophysiology of hereditary angioedema. [ABSTRACT FROM AUTHOR]

Published
2023
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6. SARS-CoV-2 Spike Protein Activates Human Lung Macrophages

Author

Francesco Palestra, Remo Poto, Renato Ciardi, Giorgia Opromolla, Agnese Secondo, Valentina Tedeschi, Anne Lise Ferrara, Rosa Maria Di Crescenzo, Maria Rosaria Galdiero, Leonardo Cristinziano, Luca Modestino, Gianni Marone, Alfonso Fiorelli, Gilda Varricchi, Stefania Loffredo, Palestra, Francesco, Poto, Remo, Ciardi, Renato, Opromolla, Giorgia, Secondo, Agnese, Tedeschi, Valentina, Ferrara, Anne Lise, Di Crescenzo, Rosa Maria Di, Galdiero, Maria Rosaria, Cristinziano, Leonardo, Modestino, Luca, Marone, Gianni, Fiorelli, Alfonso, Varricchi, Gilda, and Loffredo, Stefania

Subjects
Organic Chemistry, COVID-19, ACE2, General Medicine, Keywords: COVID-19, spike protein, Catalysis, cytokines, Computer Science Applications, macrophages, Inorganic Chemistry, cytokine, Physical and Theoretical Chemistry, Molecular Biology, Spectroscopy, TMPRSS2
Abstract

COVID-19 is a viral disease caused by SARS-CoV-2. This disease is characterized primarily, but not exclusively, by respiratory tract inflammation. SARS-CoV-2 infection relies on the binding of spike protein to ACE2 on the host cells. The virus uses the protease TMPRSS2 as an entry activator. Human lung macrophages (HLMs) are the most abundant immune cells in the lung and fulfill a variety of specialized functions mediated by the production of cytokines and chemokines. The aim of this project was to investigate the effects of spike protein on HLM activation and the expression of ACE2 and TMPRSS2 in HLMs. Spike protein induced CXCL8, IL-6, TNF-α, and IL-1β release from HLMs; promoted efficient phagocytosis; and induced dysfunction of intracellular Ca2+ concentration by increasing lysosomal Ca2+ content in HLMs. Microscopy experiments revealed that HLM tracking was affected by spike protein activation. Finally, HLMs constitutively expressed mRNAs for ACE2 and TMPRSS2. In conclusion, during SARS-CoV-2 infection, macrophages seem to play a key role in lung injury, resulting in immunological dysfunction and respiratory disease.

Published
2023

7. Size-based effects of anthropogenic ultrafine particles on activation of human lung macrophages

Author

Simone Marcella, Barbara Apicella, Agnese Secondo, Francesco Palestra, Giorgia Opromolla, Renato Ciardi, Valentina Tedeschi, Anne Lise Ferrara, Carmela Russo, Maria Rosaria Galdiero, Leonardo Cristinziano, Luca Modestino, Giuseppe Spadaro, Alfonso Fiorelli, Stefania Loffredo, Marcella, Simone, Apicella, Barbara, Secondo, Agnese, Palestra, Francesco, Opromolla, Giorgia, Ciardi, Renato, Tedeschi, Valentina, Ferrara, Anne Lise, Russo, Carmela, Rosaria Galdiero, Maria, Cristinziano, Leonardo, Modestino, Luca, Spadaro, Giuseppe, Fiorelli, Alfonso, and Loffredo, Stefania

Subjects
Air Pollutants, Monocyte-derived macrophage, PM, Macrophage, Interleukin-6, Tumor Necrosis Factor-alpha, Air pollution, ROS, Calcium homeostasi, Monocyte, Nanoparticle, Chemokine, Air Pollutant, Macrophages, Alveolar, Cytokines, Humans, Particulate Matter, Particle Size, Reactive Oxygen Species, Reactive Oxygen Specie, Cytokine, Lung, General Environmental Science, Human
Abstract

The anthropogenic particulate matter (PM), suspended air dust that can be inhaled by humans and deposited in the lungs, is one of the main pollutants in the industrialized cities atmosphere. Recent studies have shown that PM has adverse effects on respiratory diseases. These effects are mainly due to the ultrafine particles (PM0.1, PM

Published
2022

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