tetano
Editor, Senior Moderator
Sci Rep
. 2023 Jul 14;13(1):11392.
doi: 10.1038/s41598-023-38382-5. SARS-CoV-2 spike protein induces lung endothelial cell dysfunction and thrombo-inflammation depending on the C3a/C3a receptor signalling
Luca Perico[SUP] #[/SUP][SUP] 1 [/SUP], Marina Morigi[SUP] #[/SUP][SUP] 2 [/SUP], Anna Pezzotta[SUP] 2 [/SUP], Monica Locatelli[SUP] 2 [/SUP], Barbara Imberti[SUP] 2 [/SUP], Daniela Corna[SUP] 2 [/SUP], Domenico Cerullo[SUP] 2 [/SUP], Ariela Benigni[SUP] 2 [/SUP], Giuseppe Remuzzi[SUP] 2 [/SUP]
Affiliations
The spike protein of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) can interact with endothelial cells. However, no studies demonstrated the direct effect of the spike protein subunit 1 (S1) in inducing lung vascular damage and the potential mechanisms contributing to lung injury. Here, we found that S1 injection in mice transgenic for human angiotensin converting enzyme 2 (ACE2) induced early loss of lung endothelial thromboresistance at 3 days, as revealed by thrombomodulin loss and von Willebrand factor (vWF) increase. In parallel, vascular and epithelial C3 deposits and enhanced C3a receptor (C3aR) expression were observed. These changes preceded diffuse alveolar damage and lung vascular fibrin(ogen)/platelets aggregates at 7 days, as well as inflammatory cell recruitment and fibrosis. Treatment with C3aR antagonist (C3aRa) inhibited lung C3 accumulation and C3a/C3aR activation, limiting vascular thrombo-inflammation and fibrosis. Our study demonstrates that S1 triggers vascular dysfunction and activates complement system, instrumental to lung thrombo-inflammatory injury. By extension, our data indicate C3aRa as a valuable therapeutic strategy to limit S1-dependent lung pathology.
. 2023 Jul 14;13(1):11392.
doi: 10.1038/s41598-023-38382-5. SARS-CoV-2 spike protein induces lung endothelial cell dysfunction and thrombo-inflammation depending on the C3a/C3a receptor signalling
Luca Perico[SUP] #[/SUP][SUP] 1 [/SUP], Marina Morigi[SUP] #[/SUP][SUP] 2 [/SUP], Anna Pezzotta[SUP] 2 [/SUP], Monica Locatelli[SUP] 2 [/SUP], Barbara Imberti[SUP] 2 [/SUP], Daniela Corna[SUP] 2 [/SUP], Domenico Cerullo[SUP] 2 [/SUP], Ariela Benigni[SUP] 2 [/SUP], Giuseppe Remuzzi[SUP] 2 [/SUP]
Affiliations
- PMID: 37452090
- PMCID: PMC10349115
- DOI: 10.1038/s41598-023-38382-5
The spike protein of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) can interact with endothelial cells. However, no studies demonstrated the direct effect of the spike protein subunit 1 (S1) in inducing lung vascular damage and the potential mechanisms contributing to lung injury. Here, we found that S1 injection in mice transgenic for human angiotensin converting enzyme 2 (ACE2) induced early loss of lung endothelial thromboresistance at 3 days, as revealed by thrombomodulin loss and von Willebrand factor (vWF) increase. In parallel, vascular and epithelial C3 deposits and enhanced C3a receptor (C3aR) expression were observed. These changes preceded diffuse alveolar damage and lung vascular fibrin(ogen)/platelets aggregates at 7 days, as well as inflammatory cell recruitment and fibrosis. Treatment with C3aR antagonist (C3aRa) inhibited lung C3 accumulation and C3a/C3aR activation, limiting vascular thrombo-inflammation and fibrosis. Our study demonstrates that S1 triggers vascular dysfunction and activates complement system, instrumental to lung thrombo-inflammatory injury. By extension, our data indicate C3aRa as a valuable therapeutic strategy to limit S1-dependent lung pathology.