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

Autor: Palestra F; Department of Translational Medical Sciences, University of Naples Federico II, 80131 Naples, Italy., Poto R; Department of Translational Medical Sciences, University of Naples Federico II, 80131 Naples, Italy.; World Allergy Organization (WAO) Center of Excellence (CoE), 80131 Naples, Italy., Ciardi R; Department of Translational Medical Sciences, University of Naples Federico II, 80131 Naples, Italy., Opromolla G; Translational Medical and Surgical Science, University of Campania Luigi Vanvitelli, 80131 Naples, Italy., Secondo A; Department of Neuroscience, Reproductive and Odontostomatological Sciences, University of Naples Federico II, 80131 Naples, Italy., Tedeschi V; Department of Neuroscience, Reproductive and Odontostomatological Sciences, University of Naples Federico II, 80131 Naples, Italy., Ferrara AL; Department of Translational Medical Sciences, University of Naples Federico II, 80131 Naples, Italy.; Institute of Experimental Endocrinology and Oncology (IEOS), National Research Council, 80131 Naples, Italy., Di Crescenzo RM; Department of Neuroscience, Reproductive and Odontostomatological Sciences, University of Naples Federico II, 80131 Naples, Italy., Galdiero MR; Department of Translational Medical Sciences, University of Naples Federico II, 80131 Naples, Italy.; World Allergy Organization (WAO) Center of Excellence (CoE), 80131 Naples, Italy.; Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, 80131 Naples, Italy., Cristinziano L; Department of Translational Medical Sciences, University of Naples Federico II, 80131 Naples, Italy., Modestino L; Department of Translational Medical Sciences, University of Naples Federico II, 80131 Naples, Italy., Marone G; Department of Translational Medical Sciences, University of Naples Federico II, 80131 Naples, Italy.; World Allergy Organization (WAO) Center of Excellence (CoE), 80131 Naples, Italy.; Institute of Experimental Endocrinology and Oncology (IEOS), National Research Council, 80131 Naples, Italy.; Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, 80131 Naples, Italy., Fiorelli A; Translational Medical and Surgical Science, University of Campania Luigi Vanvitelli, 80131 Naples, Italy., Varricchi G; Department of Translational Medical Sciences, University of Naples Federico II, 80131 Naples, Italy.; World Allergy Organization (WAO) Center of Excellence (CoE), 80131 Naples, Italy.; Institute of Experimental Endocrinology and Oncology (IEOS), National Research Council, 80131 Naples, Italy.; Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, 80131 Naples, Italy., Loffredo S; Department of Translational Medical Sciences, University of Naples Federico II, 80131 Naples, Italy.; World Allergy Organization (WAO) Center of Excellence (CoE), 80131 Naples, Italy.; Institute of Experimental Endocrinology and Oncology (IEOS), National Research Council, 80131 Naples, Italy.; Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, 80131 Naples, Italy.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2023 Feb 03; Vol. 24 (3). Date of Electronic Publication: 2023 Feb 03.
DOI: 10.3390/ijms24033036
Abstrakt: 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 Ca 2+ concentration by increasing lysosomal Ca 2+ 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.
Databáze: MEDLINE
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