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Extracellular Histone (None)
- Target
- None
- Molecular classification
- Protein complex, Damage-associated molecular pattern (DAMP)
01
Overview
Extracellular histones are nuclear proteins that, when released outside the cell, act as potent damage-associated molecular patterns (DAMPs) involved in inflammation and tissue injury. They are released during cell death, NETosis, or cellular stress and can exist as free proteins, DNA-bound nucleosomes, or components of NETs. They activate immune cells via TLR2/4/9 and P2XR7 receptors, leading to pro-inflammatory cytokine release, endothelial dysfunction, and thrombosis. Elevated levels are implicated in various critical illnesses, making them a therapeutic target for intervention.
02
Mechanism of action
Blocking release from dying cells or NETs formation; Neutralizing circulating histones; Inhibiting downstream signaling pathways (e.g., TLR)
03
Biological functions
Immune responseInflammationCell deathEndothelial dysfunctionThrombosis
04
Disease associations
SepsisTrauma-induced organ failureAcute liver failureARDS/lung dysfunctionMyocardial infarction/reperfusion injuryAutoimmune diseases
05
Safety considerations
Potential for broad immunosuppressionOff-target effects of TLR antagonistsRebound inflammation upon drug withdrawal
06
Interacting drugs
Antibodies (anti-histone)
3 more in the full profile.
07
Biomarkers
Elevated levels of extracellular histones correlate with worse clinical outcomes
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