SARS-CoV-2 Spike Protein Activates Human Lung Macrophages

被引：13

作者：

Palestra, Francesco ^{[1
]}

Poto, Remo ^{[1
,2
]}

Ciardi, Renato ^{[1
]}

Opromolla, Giorgia ^{[3
]}

Secondo, Agnese ^{[4
]}

Tedeschi, Valentina ^{[4
]}

Ferrara, Anne Lise ^{[1
,5
]}

Di Crescenzo, Rosa Maria ^{[4
]}

Galdiero, Maria Rosaria ^{[1
,2
,6
]}

Cristinziano, Leonardo ^{[1
]}

Modestino, Luca ^{[1
]}

Marone, Gianni ^{[1
,2
,5
,6
]}

Fiorelli, Alfonso ^{[3
]}

Varricchi, Gilda ^{[1
,2
,5
,6
]}

Loffredo, Stefania ^{[1
,2
,5
,6
]}

机构：

[1] Univ Naples Federico II, Dept Translat Med Sci, I-80131 Naples, Italy

[2] World Allergy Org WAO, Ctr Excellence CoE, I-80131 Naples, Italy

[3] Univ Campania Luigi Vanvitelli, Translat Med & Surg Sci, I-80131 Naples, Italy

[4] Univ Naples Federico II, Dept Neurosci Reprod & Odontostomatol Sci, I-80131 Naples, Italy

[5] CNR, Inst Expt Endocrinol & Oncol IEOS, I-80131 Naples, Italy

[6] Univ Naples Federico II, Ctr Basic & Clin Immunol Res CISI, I-80131 Naples, Italy

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2023年 / 24卷 / 03期

关键词：

COVID-19; spike protein; ACE2; TMPRSS2; cytokines; macrophages; POLARIZATION; MYOCARDITIS; PLASTICITY; RELEASE; CELLS;

D O I：

10.3390/ijms24033036

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：

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-alpha, and IL-1 beta 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.

引用

页数：14

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