Platelet-Activating Factor Signaling in Inflammation and Disease

Platelet-Activating Factor (PAF) is a potent glycerophosphocholine lipid mediator with central roles in physiological homeostasis and pathological inflammation. Synthesised via both a de novo pathway and a rapid remodelling route, PAF acts through its G-protein-coupled receptor (PAFR) to trigger a cascade of intracellular signals, including phospholipase activation, calcium mobilisation and downstream MAPK, PI3K–AKT and NF-κB pathways. These events drive leukocyte recruitment, vascular permeability, platelet aggregation and cytokine release in acute inflammation. Chronic PAF signalling contributes to the pathogenesis of a wide spectrum of diseases, from cardiovascular disorders and atherosclerosis to cancer progression, neuroinflammation and tissue injury after radiotherapy. Counter-regulatory enzymes such as PAF acetylhydrolases (PAF-AHs) modulate PAF tone by hydrolysing the sn-2 acetate group, thereby limiting exuberant responses. The balance between PAF generation and degradation underpins its systemic impact, rendering components of the PAF signalling axis attractive targets for therapeutic intervention. Recent advances have elucidated molecular interactions between PAFR and other receptor systems, uncovered PAF’s role in extracellular vesicle biology, and revealed novel protective or deleterious roles in organ-specific contexts. These insights continue to inform strategies to modulate PAF activity in inflammation-driven diseases.

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Platelet-Activating Factor Signaling in Inflammation and Disease publication trend

The graph below shows the total number of articles in platelet-activating factor signaling in inflammation and disease across all publications each year (not limited to Nature Index journals).

Technical terms

Platelet-Activating Factor (PAF): A glycerophosphocholine lipid mediator responsible for initiating inflammatory and thrombotic responses through PAFR activation.

PAF Receptor (PAFR): A G-protein-coupled receptor that binds PAF and mediates downstream signalling cascades in immune, vascular and neuronal cells.

PAF Acetylhydrolase (PAF-AH): Enzymes that hydrolyse the acetyl group at the sn-2 position of PAF, thus terminating PAF’s biological activity.

Glycerophosphocholine: The phospholipid backbone of PAF, comprising a glycerol moiety linked to phosphocholine and various fatty acyl chains.

References

1. PLA2G7/PAF-AH as Potential Negative Regulator of the Wnt Signaling Pathway Mediates Protective Effects in BRCA1 Mutant Breast Cancer. International Journal of Molecular Sciences (2023).
2. Platelet-activating factor receptor (PAFR) regulates neuronal maturation and synaptic transmission during postnatal retinal development. Frontiers in Cellular Neuroscience (2024).
3. Ultraviolet B Radiation Generates Platelet-activating Factor-like Phospholipids underlying Cutaneous Damage*. Journal of Biological Chemistry (2005).
4. Platelet-activating factor (PAF) receptor as a promising target for cancer cell repopulation after radiotherapy. Oncogenesis (2017).
5. New Insights Into the Pathologic Roles of the Platelet-Activating Factor System. Frontiers in Endocrinology (2021).