The platelet NLRP3 inflammasome is upregulated in sickle cell disease patients

Authors

• T Arora
• X Wang
• SL Thein
• S Vogel

Abstract

Sickle cell disease (SCD) is linked with a hypercoagulable state, and activated platelets play an important role in this pathology. It has been shown recently that the nucleotide-binding domain leucine rich repeat containing protein (NLRP3) inflammasome in platelets promotes platelet activation and aggregation. Activation of NLRP3 typically upregulates caspase-1 activity and promotes cleavage and secretion of IL-1ß in immune cells, which is a critical inflammatory process. We investigated the effect of SCD on the platelet NLRP3 inflammasome. Platelets were isolated from whole blood derived from SCD patients at steady state and crisis, and healthy volunteers. We measured platelet NLRP3-dependent caspase-1 activity and cleavage and secretion of IL-1ß with FLICA, western blot, and ELISA, respectively. Caspase 1 activity as well as IL1ß cleavage and secretion in platelets were significantly upregulated in SCD patients at steady state and further upregulated in crisis, which was in part suppressed by the NLRP3 inhibitor MCC950. In conclusion, the platelet NLRP3 inflammasome is upregulated in the context of SCD. Further studies are required to study the potential therapeutic implications of platelet NLRP3-dependent effects in SCD.

Scientific Focus Area: Immunology

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