Extracellular Purine Nucleotides and Phosphorylated Molecular Patterns (eATP/PAMPs)

Extracellular Purine Nucleotides and Phosphorylated Molecular Patterns are a heterogeneous group of signaling molecules that act as potent triggers for the innate immune system (Di Virgilio et al., 2020). Adenosine triphosphate (ATP) and adenosine diphosphate (ADP), while primarily intracellular, are released into the extracellular space during cell stress or necrosis, where they function as Damage-Associated Molecular Patterns (DAMPs) by activating purinergic P2 receptors (Trautmann, 2009). Similarly, phosphorylated Pathogen-Associated Molecular Patterns (PAMPs), such as the lipid A component of bacterial lipopolysaccharide (LPS), initiate inflammatory cascades through Toll-like receptors (Peters et al., 2014). In pathological conditions like sepsis and acute kidney injury, the systemic accumulation of these phosphorylated molecules drives hyper-inflammation and organ failure. Therapeutic interventions, such as the administration of alkaline phosphatase (e.g., ilofolstat), target these molecules by enzymatically removing their phosphate groups (Pickkers et al., 2018). This dephosphorylation detoxifies endotoxins and converts pro-inflammatory ATP into adenosine, which exerts anti-inflammatory and tissue-protective effects.

Other names

Extracellular nucleotidesPhosphorylated Damage-Associated Molecular PatternsPhosphorylated Pathogen-Associated Molecular PatternsDanger signalsAlarminseATPeADP

Enzymatic dephosphorylation and detoxification of pro-inflammatory ligands into non-toxic or anti-inflammatory metabolites.