Neutrophil extracellular traps and inflammasomes cooperatively promote venous thrombosis in mice

Journal article

Abstract Deep vein thrombosis (DVT) is linked to local inflammation. A role for both neutrophil extracellular traps (NETs) and the assembly of inflammasomes (leading to caspase-1–dependent interleukin-1β activation) in the development of DVT was recently suggested. However, no link between these 2 processes in the setting of thrombosis has been investigated. Here, we demonstrate that stimulation of neutrophils induced simultaneous formation of NETs and active caspase-1. Caspase-1 was largely associated with NETs, suggesting that secreted active caspase-1 requires NETs as an adhesive surface. NETs and their components, histones, promoted robust caspase-1 activation in platelets with the strongest effect exerted by histones 3/4. Murine DVT thrombi contained active caspase-1, which peaked at 6 hours when compared with 48-hour thrombi. Platelets constituted more than one-half of cells containing active caspase-1 in dissociated thrombi. Using intravital microscopy, we identified colocalized NETs and caspase-1 as well as platelet recruitment at the site of thrombosis. Pharmacological inhibition of caspase-1 strongly reduced DVT in mice, and thrombi that still formed contained no citrullinated histone 3, a marker of NETs. Taken together, these data demonstrate a cross-talk between NETs and inflammasomes both in vitro and in the DVT setting. This may be an important mechanism supporting thrombosis in veins.

Authors: Campos, J; Ponomaryov, T; De Prendergast, A; Whitworth, K; Smith, CW

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: American Society of Hematology (ASH Publications)
• Journal: Blood Advances
• Volume: 5
• Issue: 9
• Pages: 2319-2324
• Publication date: 2021-05-03
• DOI: 10.1182/bloodadvances.2020003377
• EISSN: 2473-9537
• ISSN: 2473-9529
• Language: English
• Keywords: Neutrophil Extracellular Traps