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

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 3

SARS-CoV-2 spike protein activated platelets via 2 distinct signaling pathways.

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SARS-CoV-2 spike protein activated platelets via 2 distinct signaling pa...
(A) Purified platelets from healthy donors (n = 5) were incubated with spike protein or S-pseudovirus. Phosphorylation of PKC-substrates (pPKC-Subs, assessed PKC activation through the resulting phosphorylation of PKC substrates on specific serine residues) and Akt (pAkt) were detected by Western blot. TRAP was used as the positive control. (B) Purified platelets (n = 5) were pretreated with indicated inhibitors before incubation with spike protein. Phosphorylation of pPKC-Subs or Akt shown. (C) Purified platelets (n = 3) were pretreated with isotype or CD42b antibodies before incubation by spike protein. Phosphorylation of pPKC-Subs or Akt shown. (D) Purified platelets (n = 4) were pretreated with Ro31-8220 or LY294002 before incubation with spike protein or S-pseudovirus. P selectin and CD40L expression measured by flow cytometry. Comparisons between groups were measured by paired Student’s t test in A and C, or 1-way ANOVA with Dunnett’s multiple-comparison test in B and D. Mean with SD and P value are displayed. *P < 0.05; **P < 0.01; ***P < 0.001. **** P < 0.0001.