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 1

SARS-CoV-2–induced platelet-monocyte aggregation and P selectin/CD40L expression on platelets by spike protein.

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SARS-CoV-2–induced platelet-monocyte aggregation and P selectin/CD40L ex...
(A) PKH26- or CFSE-labeled platelets from healthy donors (n = 5) were mixed at 1:1 and incubated with increasing concentrations of spike protein or S-pseudovirus, and aggregates were detected by flow cytometry. Double-colored events indicated the platelet aggregation, and TRAP was used as the positive control. (B) Peripheral blood from healthy donors (n = 5) was stimulated by spike protein or S-pseudovirus at indicated concentration and analyzed by flow cytometry. Platelet-monocyte aggregation was evaluated using the percentage of CD42b+/CD14+ cells. (C) Platelet-monocyte aggregation was visualized by fluorescence microscopy; scale bar: 20 μm. (D) Purified platelets from healthy donors (n = 5) were incubated with spike protein or S-pseudovirus. P selectin, CD40L expression, and fibrinogen binding were shown by histogram and MFI. (E) Purified platelets (n = 4) were pretreated with isotype antibody (indicated as control) or anti-spike RBD before incubation with S-pseudovirus; P selectin and CD40L expression are shown. Mean with SD and P value by paired Student’s t test are displayed. *P < 0.05; **P < 0.01; ***P < 0.001.