Platelets mediate inflammatory monocyte activation by SARS-CoV-2 spike protein
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
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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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 5

SARS-COV-2–activated platelets mediated inflammatory monocyte activation through the engagement of P selectin/PGSL-1 and CD40L/CD40.

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SARS-COV-2–activated platelets mediated inflammatory monocyte activation...
(A) Peripheral blood from healthy donors (n = 3) was stimulated by spike protein or S-pseudovirus in the presence of anti–P selectin or anti–PSGL-1. Platelet-monocyte aggregation was evaluated using the percentage of CD42b+/CD14+ cells. (B) Anti–P selectin or anti-CD40L was added into monocyte-platelet cocultures with spike protein or S-pseudovirus. IL-1β expression in monocytes (n = 4) was measured. (C) Purified monocytes (n = 3) were cultured with/without recombinant P selectin and/or CD40L, and their expression of IL-1β and IL-10 is shown. Mean with SD and P value by paired Student’s t test are displayed. *P < 0.05.