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Target intelligence / Profile preview
Extracellular Histone H4
- Molecular classification
- Protein, DAMP
01
Overview
Extracellular Histone H4 is a core histone protein released into the extracellular space during cell death or tissue injury. It acts as a damage-associated molecular pattern (DAMP), triggering immune responses, cytotoxicity, and inflammation. It has been implicated in organ failure during sepsis and other critical illnesses, acting via membrane permeabilization, TLR/NLRP3 pathway activation, and Ca²⁺ influx. Neutralizing antibodies and polyanionic drugs are under investigation as therapeutic strategies.
02
Mechanism of action
Membrane permeabilization; TLR2/TLR4/NLRP3 pathway activation; Ca²⁺ influx
03
Biological functions
Immune activationNeutrophil activationEndothelial dysfunctionPlatelet activationComplement system interactionInflammation
04
Disease associations
SepsisOrgan failureAcute lung injuryAcute liver injuryThrombosisEndothelial dysfunction
05
Safety considerations
Potential for broad immune activationOff-target effects of neutralizing agents
06
Biomarkers
SepsisOrgan failure
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