The National Institutes of Health found that the key factor of the new coronavirus-induced thrombotic inflammation is expected to reduce the thrombotic inflammation and acute sequelae caused by the new coronary pneumonia
source:National Institutes of Health
File date:112-07-17
Update time:112-07-17
COVID-19 has been raging around the world for more than 3 years. Although the global epidemic is now slowing down, there are still many patients who have been diagnosed with severe inflammation or even died. Thromboinflammation is the main cause of the lesions and death of confirmed diseases. Thromboinflammation refers to blood coagulation combined with inflammation. In the autopsy of confirmed patients, it was found that there were blood clots rich in platelets and microangiopathy in various organs ( small vessel abnormalities). Persistent microclots were also found in the plasma of acutely diagnosed patients and patients with COVID-19. However, the exact molecular mechanism by which SARS-CoV-2 induces thrombotic inflammation remains unclear.
The research team of Xie Shiliang, a distinguished researcher at the Immunomedicine Research Center of the National Institutes of Health, found that spleen tyrosine kinase (Spleen tyrosine kinase, Syk) coupled with C-type lectin receptor 2 (CLEC2) binds to the receptor of the spike protein of the new coronavirus Domain (RBD) has a direct interaction, causing neutrophil activation to produce aggregated (aggregated) neutrophil extracellular traps (neutrophil extracellular traps, NETs), and then lead to lung inflammation and damage. And it has been confirmed in animal experiments that the recombinant CLEC2 protein (CLEC2.Fc) can reduce thrombus inflammation in mice, and it is expected to be applied to the treatment of patients diagnosed with the new crown. This research result was published in the international journal “EMBO Molecular Medicine” in May of this year (112).
CLEC2 is a receptor that is abundantly expressed on platelets and alveolar macrophages. In past studies, it was found that CLEC2 binds to different pathogens, activates platelets to produce NETs, causes microclots in different organs, and then triggers excessive inflammation. The mechanisms of dengue fever and tumor metastasis are all related. The research team found that the aggregated NETs produced by the combination of CLEC2 and 2019-nCoV are different from the typical NETs with a network structure in the past, and in the absence of CLEC2 platelets, 2019-nCoV cannot cause NETs. The research team further used the lentivirus expressing the RBD of the new coronavirus to stimulate platelets and neutrophils, and confirmed that the new coronavirus activates platelets through the combination of RBD and CLEC2 to increase the production of NETs.
In order to assess the potential therapeutic significance of these findings, the research team injected recombinant CLEC2 protein (CLEC2.Fc) into mice infected with the new coronavirus (AAV-hACE2-infected mice), and found that CLEC2.Fc can effectively inhibit the pathogenesis of the new coronavirus after infection. NETs in the lung and heart, and reduced thrombotic inflammation in mice. This indicates that CLEC2 can serve as a novel pattern recognition receptor for the new coronavirus, and CLEC2.Fc is expected to be used as a therapeutic agent against thrombotic inflammation caused by the new coronavirus, and may reduce the incidence of acute sequelae (post-acute sequelae of COVID-19, PASC). risk.
Full research paper:https://doi.org/10.15252/emmm.202216351
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