ArticleInternational journal of molecular sciences2023
SARS-CoV-2 Spike Proteins and Cell-Cell Communication Induce P-Selectin and Markers of Endothelial Injury, NETosis, and Inflammation in Human Lung Microvascular Endothelial Cells and Neutrophils: Implications for the Pathogenesis of COVID-19 Coagulopathy.
Article in International journal of molecular sciences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 22 citations in OpenAlex.
- Elevated risk of first-time pulmonary hypertension among COVID-19 survivors: a 4.5-year longitudinal study.ERJ open research · 2026Article
- WWC1 deficiency exacerbates sepsis-induced lung injury by promoting NETosis, M1 and M2b macrophage recruitment, and pyroptosis via YAP1 and STING pathways.Journal of inflammation (London, England) · 2026Article
- Targeting the GPX4-FUNDC1 Interaction with Magnesium Lithospermate B Attenuates Sepsis-Associated Lung Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Endothelial Cell Activation by SARS-CoV-2 Spike Protein and Its RBD: Central Player of the Immunothrobotic Response in COVID-19.Current issues in molecular biology · 2026Article
- Unraveling the cardiovascular burden of long COVID: symptom profiles, underlying mechanisms, and clinical management insights.Frontiers in cardiovascular medicine · 2026Review
- Insight to Neglected Biomarkers in COVID-19: A Comprehensive Narrative Review".Biomarker insights · 2026Review
- Engineered Dual-Function Antibody-Like Proteins to Combat SARS-CoV-2-Induced Immune Dysregulation and Inflammation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Biomarkers of Endothelial Damage and Disease Severity in COVID-19 Patients.Current issues in molecular biology · 2025Article
- No Evidence of Direct Activation of Human Neutrophil Responses by Multivalent Prefusion Trimeric SARS-CoV-2 Spike ProteinbioRxiv : the preprint server for biology · 2025Article
- No evidence of direct activation of human neutrophil responses by multivalent prefusion trimeric SARS-CoV-2 Spike protein ex vivo.PloS one · 2025Article
- Mechanisms of lung endothelial cell injury and survival in pulmonary arterial hypertension.American journal of physiology. Lung cellular and molecular physiology · 2024Review
- Trivalent Disulfide Unit-Masked System Efficiently Delivers Large Oligonucleotide.Molecules (Basel, Switzerland) · 2024Article
- Impaired instructive and protective barrier functions of the endothelial cell glycocalyx pericellular matrix is impacted in COVID-19 disease.Journal of cellular and molecular medicine · 2024Review
- Special Issue "COVID-19 Coagulopathy: Advances on Pathophysiology and Therapies".International journal of molecular sciences · 2024Article
- Recombinant Rod Domain of Vimentin Reduces SARS-CoV-2 Viral Replication by Blocking Spike Protein-ACE2 Interactions.International journal of molecular sciences · 2024Article
- The Ways of the Virus: Interactions of Platelets and Red Blood Cells with SARS-CoV-2, and Their Potential Pathophysiological Significance in COVID-19.International journal of molecular sciences · 2023Review
- Short Survey on the Protein Modifications in Plasma during SARS-CoV-2 Infection.International journal of molecular sciences · 2023Article
- Symmetrical peripheral gangrene: potential mechanisms and therapeutic approaches in severe COVID-19.Frontiers in cardiovascular medicine · 2023Review
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
COVID-19 progression often involves severe lung injury, inflammation, coagulopathy, and leukocyte infiltration into pulmonary tissues. The pathogenesis of these complications is unknown. Because vascular endothelium and neutrophils express angiotensin-converting enzyme-2 and spike (S)-proteins, which are present in bodily fluids and tissues of SARS-CoV-2-infected patients, we investigated the effect of S-proteins and cell-cell communication on human lung microvascular endothelial cells and neutrophils expression of P-selectin, markers of coagulopathy, NETosis, and inflammation. Exposure of endothelial cells or neutrophils to S-proteins and endothelial-neutrophils co-culture induced P-selectin transcription and expression, significantly increased expression/secretion of IL-6, von Willebrand factor (vWF, pro-coagulant), and citrullinated histone H3 (cit-H3, NETosis marker). Compared to the SARS-CoV-2 Wuhan variant, Delta variant S-proteins induced 1.4-15-fold higher P-selectin and higher IL-6 and vWF. Recombinant tissue factor pathway inhibitor (rTFPI), 5,5'-dithio-bis-(2-nitrobenzoic acid) (thiol blocker), and thrombomodulin (anticoagulant) blocked S-protein-induced vWF, IL-6, and cit-H3. This suggests that following SARS-CoV-2 contact with the pulmonary endothelium or neutrophils and endothelial-neutrophil interactions, S-proteins increase adhesion molecules, induce endothelial injury, inflammation, NETosis and coagulopathy via the tissue factor pathway, mechanisms involving functional thiol groups, and/or the fibrinolysis system. Using rTFPI, effectors of the fibrinolysis system and/or thiol-based drugs could be viable therapeutic strategies against SARS-CoV-2-induced endothelial injury, inflammation, NETosis, and coagulopathy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.