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Platelets mediate inflammatory monocyte activation by SARS-CoV-2 spike protein
Tianyang Li, … , Ian N. Crispe, Zhengkun Tu
Tianyang Li, … , Ian N. Crispe, Zhengkun Tu
Published December 29, 2021
Citation Information: J Clin Invest. 2022;132(4):e150101. https://doi.org/10.1172/JCI150101.
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Research Article Inflammation

Platelets mediate inflammatory monocyte activation by SARS-CoV-2 spike protein

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Abstract

Infection with SARS-CoV-2, the causative agent of COVID-19, causes mild to moderate disease in most patients but carries a risk of morbidity and mortality. Seriously affected individuals manifest disorders of hemostasis and a cytokine storm, but it is not understood how these manifestations of severe COVID-19 are linked. Here, we showed that the SARS-CoV-2 spike protein engaged the CD42b receptor to activate platelets via 2 distinct signaling pathways and promoted platelet-monocyte communication through the engagement of P selectin/PGSL-1 and CD40L/CD40, which led to proinflammatory cytokine production by monocytes. These results explain why hypercoagulation, monocyte activation, and a cytokine storm are correlated in patients severely affected by COVID-19 and suggest a potential target for therapeutic intervention.

Authors

Tianyang Li, Yang Yang, Yongqi Li, Zhengmin Wang, Faxiang Ma, Runqi Luo, Xiaoming Xu, Guo Zhou, Jianhua Wang, Junqi Niu, Guoyue Lv, Ian N. Crispe, Zhengkun Tu

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Figure 2

SARS-CoV-2 spike protein engaged with CD42b to induce P selectin/CD40L expression on platelets.

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SARS-CoV-2 spike protein engaged with CD42b to induce P selectin/CD40L e...
(A) Purified platelets from healthy donors (n = 3) were incubated with or without spike protein, and Western blot analysis was performed using indicated antibody after IP for spike protein (IP lane). Density of IP lane was analyzed. (B) Purified platelets (n = 3) were pretreated with indicated antibody before incubation with spike protein; spike protein on platelets detected by Western blot. (C and D) Purified platelets were pretreated with anti-CD42b or isotype antibody before incubation by spike protein or S-pseudovirus; spike protein binding (n = 5) and the expressions of P selectin and CD40L (n = 4) on platelets were examined by flow cytometry. As anti-CD42b control, red controls were indicated as spike protein and isotype antibody; blue controls indicated as S-pseudovirus and isotype antibody. (E) Recombinant S-RBD was incubated with ACE-2 or CD42b, and their interaction was measured by co-IP. (F) Fixed platelets were incubated with S-RBD, and platelet-vWF complexes were detected by flow cytometry using recombinant vWF and ristocetin. Comparisons were made with paired Student’s t test, except in B, which was assessed by 1-way ANOVA with Dunnett’s multiple-comparison test. Mean with SD and P value are displayed. *P < 0.05; **P < 0.01; ***P < 0.001.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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