PMID- 36769357
OWN - NLM
STAT- MEDLINE
DCOM- 20230214
LR  - 20231106
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 24
IP  - 3
DP  - 2023 Feb 3
TI  - SARS-CoV-2 Spike Protein Activates Human Lung Macrophages.
LID - 10.3390/ijms24033036 [doi]
LID - 3036
AB  - 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-1beta 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.
FAU - Palestra, Francesco
AU  - Palestra F
AUID- ORCID: 0000-0001-6145-7475
AD  - Department of Translational Medical Sciences, University of Naples Federico II, 
      80131 Naples, Italy.
FAU - Poto, Remo
AU  - Poto R
AUID- ORCID: 0000-0002-4723-0167
AD  - Department of Translational Medical Sciences, University of Naples Federico II, 
      80131 Naples, Italy.
AD  - World Allergy Organization (WAO) Center of Excellence (CoE), 80131 Naples, Italy.
FAU - Ciardi, Renato
AU  - Ciardi R
AUID- ORCID: 0000-0003-3815-426X
AD  - Department of Translational Medical Sciences, University of Naples Federico II, 
      80131 Naples, Italy.
FAU - Opromolla, Giorgia
AU  - Opromolla G
AUID- ORCID: 0000-0001-8698-0238
AD  - Translational Medical and Surgical Science, University of Campania Luigi 
      Vanvitelli, 80131 Naples, Italy.
FAU - Secondo, Agnese
AU  - Secondo A
AUID- ORCID: 0000-0001-5054-4098
AD  - Department of Neuroscience, Reproductive and Odontostomatological Sciences, 
      University of Naples Federico II, 80131 Naples, Italy.
FAU - Tedeschi, Valentina
AU  - Tedeschi V
AUID- ORCID: 0000-0002-6540-4730
AD  - Department of Neuroscience, Reproductive and Odontostomatological Sciences, 
      University of Naples Federico II, 80131 Naples, Italy.
FAU - Ferrara, Anne Lise
AU  - Ferrara AL
AUID- ORCID: 0000-0003-1839-8873
AD  - Department of Translational Medical Sciences, University of Naples Federico II, 
      80131 Naples, Italy.
AD  - Institute of Experimental Endocrinology and Oncology (IEOS), National Research 
      Council, 80131 Naples, Italy.
FAU - Di Crescenzo, Rosa Maria
AU  - Di Crescenzo RM
AUID- ORCID: 0000-0003-0404-0141
AD  - Department of Neuroscience, Reproductive and Odontostomatological Sciences, 
      University of Naples Federico II, 80131 Naples, Italy.
FAU - Galdiero, Maria Rosaria
AU  - Galdiero MR
AUID- ORCID: 0000-0002-8086-9130
AD  - Department of Translational Medical Sciences, University of Naples Federico II, 
      80131 Naples, Italy.
AD  - World Allergy Organization (WAO) Center of Excellence (CoE), 80131 Naples, Italy.
AD  - Center for Basic and Clinical Immunology Research (CISI), University of Naples 
      Federico II, 80131 Naples, Italy.
FAU - Cristinziano, Leonardo
AU  - Cristinziano L
AUID- ORCID: 0000-0002-7835-2212
AD  - Department of Translational Medical Sciences, University of Naples Federico II, 
      80131 Naples, Italy.
FAU - Modestino, Luca
AU  - Modestino L
AUID- ORCID: 0000-0003-2063-7124
AD  - Department of Translational Medical Sciences, University of Naples Federico II, 
      80131 Naples, Italy.
FAU - Marone, Gianni
AU  - Marone G
AUID- ORCID: 0000-0002-9849-4701
AD  - Department of Translational Medical Sciences, University of Naples Federico II, 
      80131 Naples, Italy.
AD  - World Allergy Organization (WAO) Center of Excellence (CoE), 80131 Naples, Italy.
AD  - Institute of Experimental Endocrinology and Oncology (IEOS), National Research 
      Council, 80131 Naples, Italy.
AD  - Center for Basic and Clinical Immunology Research (CISI), University of Naples 
      Federico II, 80131 Naples, Italy.
FAU - Fiorelli, Alfonso
AU  - Fiorelli A
AUID- ORCID: 0000-0002-0628-613X
AD  - Translational Medical and Surgical Science, University of Campania Luigi 
      Vanvitelli, 80131 Naples, Italy.
FAU - Varricchi, Gilda
AU  - Varricchi G
AUID- ORCID: 0000-0002-9285-4657
AD  - Department of Translational Medical Sciences, University of Naples Federico II, 
      80131 Naples, Italy.
AD  - World Allergy Organization (WAO) Center of Excellence (CoE), 80131 Naples, Italy.
AD  - Institute of Experimental Endocrinology and Oncology (IEOS), National Research 
      Council, 80131 Naples, Italy.
AD  - Center for Basic and Clinical Immunology Research (CISI), University of Naples 
      Federico II, 80131 Naples, Italy.
FAU - Loffredo, Stefania
AU  - Loffredo S
AUID- ORCID: 0000-0002-5871-1898
AD  - Department of Translational Medical Sciences, University of Naples Federico II, 
      80131 Naples, Italy.
AD  - World Allergy Organization (WAO) Center of Excellence (CoE), 80131 Naples, Italy.
AD  - Institute of Experimental Endocrinology and Oncology (IEOS), National Research 
      Council, 80131 Naples, Italy.
AD  - Center for Basic and Clinical Immunology Research (CISI), University of Naples 
      Federico II, 80131 Naples, Italy.
LA  - eng
GR  - Not available/CISI Lab Project (University of Naples Federico II)/
GR  - Not available/TIMING Project (Regione Campania)/
GR  - Not available/Campania Bioscience (Regione Campania)/
GR  - (ID. project 25123)/MIUR PRIN 2017 M8Y MR8_005 and AIRC - MFAG 2020/
PT  - Journal Article
DEP - 20230203
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (spike protein, SARS-CoV-2)
RN  - 0 (Spike Glycoprotein, Coronavirus)
RN  - EC 3.4.17.23 (Angiotensin-Converting Enzyme 2)
SB  - IM
MH  - Humans
MH  - *COVID-19/metabolism
MH  - Spike Glycoprotein, Coronavirus/metabolism
MH  - SARS-CoV-2/metabolism
MH  - Angiotensin-Converting Enzyme 2/metabolism
MH  - Lung/metabolism
MH  - Macrophages/metabolism
PMC - PMC9917796
OTO - NOTNLM
OT  - ACE2
OT  - COVID-19
OT  - TMPRSS2
OT  - cytokines
OT  - macrophages
OT  - spike protein
COIS- The authors declare no conflict of interest.
EDAT- 2023/02/12 06:00
MHDA- 2023/02/15 06:00
PMCR- 2023/02/03
CRDT- 2023/02/11 01:26
PHST- 2023/01/16 00:00 [received]
PHST- 2023/01/30 00:00 [revised]
PHST- 2023/02/01 00:00 [accepted]
PHST- 2023/02/11 01:26 [entrez]
PHST- 2023/02/12 06:00 [pubmed]
PHST- 2023/02/15 06:00 [medline]
PHST- 2023/02/03 00:00 [pmc-release]
AID - ijms24033036 [pii]
AID - ijms-24-03036 [pii]
AID - 10.3390/ijms24033036 [doi]
PST - epublish
SO  - Int J Mol Sci. 2023 Feb 3;24(3):3036. doi: 10.3390/ijms24033036.