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Updated: Jun 5, 2025
Comprehensive Analysis of Procoagulant Platelets Exhibiting Features of Necrosis, Apoptosis and Platelet Activation
Published on: May 23, 2025
Platelets accelerate lipid peroxidation and induce pathogenic neutrophil extracellular trap release
Madoka Ono1, Masayasu Toyomoto2, Momono Yamauchi1
1Department of Anatomy and Developmental Biology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan; Department of Drug Discovery Medicine, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan.
Platelets promote harmful neutrophil extracellular trap (NET) formation by increasing iron and lipid peroxidation. Capsaicin, an inhibitor of lipid peroxidation, effectively suppressed NETosis in vitro and in vivo, offering a potential therapeutic strategy.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- Neutrophil extracellular traps (NETs) are crucial for host defense but excessive NETosis contributes to diseases like sepsis.
- Platelets play a role in the pathological activation of NETosis.
Purpose of the Study:
- To investigate the mechanism by which platelets induce NETosis.
- To identify and evaluate compounds that inhibit platelet-mediated pathogenic NETosis.
Main Methods:
- Co-stimulation of neutrophils with lipopolysaccharide and platelets in vitro.
- Screening for lipid peroxidation inhibitors.
- In vitro and in vivo assessment of capsaicin's effect on NETosis and lipid peroxidation.
Main Results:
- Platelets induce iron accumulation and lipid peroxidation in neutrophils, promoting NETosis.
- Capsaicin (8-methyl-N-geranyl-6-nonamide) inhibited lipid peroxidation and suppressed NETosis in vitro.
- Capsaicin attenuated lipopolysaccharide-induced NETosis in a mouse lung inflammation model.
Conclusions:
- Platelet-induced NETosis is mediated by iron accumulation and lipid peroxidation.
- Targeting lipid peroxidation with capsaicin offers a novel therapeutic approach for NETosis-related diseases.
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