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Experimental Model of Pulmonary Inflammation Induced by SARS-CoV-2 Spike Protein and Endotoxin

[Image: see text] COVID-19 is characterized by a dysregulated and excessive inflammatory response and, in severe cases, acute respiratory distress syndrome. We have recently demonstrated a previously unknown high-affinity interaction between the SARS-CoV-2 spike (S) protein and bacterial lipopolysac...

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Detalles Bibliográficos
Autores principales: Puthia, Manoj, Tanner, Lloyd, Petruk, Ganna, Schmidtchen, Artur
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2022
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9239546/
https://www.ncbi.nlm.nih.gov/pubmed/35774232
http://dx.doi.org/10.1021/acsptsci.1c00219
Descripción
Sumario:[Image: see text] COVID-19 is characterized by a dysregulated and excessive inflammatory response and, in severe cases, acute respiratory distress syndrome. We have recently demonstrated a previously unknown high-affinity interaction between the SARS-CoV-2 spike (S) protein and bacterial lipopolysaccharide (LPS), leading to the boosting of inflammation. Here we present a mouse inflammation model employing the coadministration of aerosolized S protein together with LPS to the lungs. Using NF-κB-RE-Luc reporter and C57BL/6 mice followed by combinations of bioimaging, cytokine, chemokine, fluorescence-activated cell sorting, and histochemistry analyses, we show that the model yields severe pulmonary inflammation and a cytokine profile similar to that observed in COVID-19. Therefore, the model offers utility for analyses of the pathophysiological features of COVID-19 and the development of new treatments.