Platelet-activating factor, also known as PAF, PAF-acether or AGEPC (acetyl-glyceryl-ether-phosphorylcholine), is a potent phospholipid activator and mediator of many leukocyte functions, platelet aggregation and degranulation, inflammation, and anaphylaxis.
It is also involved in changes to vascular permeability, the oxidative burst, chemotaxis of leukocytes, as well as augmentation of arachidonic acid metabolism in phagocytes.
Benveniste made significant contributions in the role and characteristics of PAF and its importance in inflammatory response and mediation.
Using lab rats and mice, he found that ionophore A23187 (a mobile ion carrier that allows the passage of Mn2+, Ca2+ and Mg2+ and has antibiotic properties against bacteria and fungi) caused the release of PAF.
His experiment’s data found that atherosclerosis (the accumulation of lipid-rich lesions in the endothelium of the arteries) can be attributed to PAF and PAF-like lipids, and identified biologically active compounds in the polar lipid fractions of olive oil, honey, milk and yoghurt, mackerel, and wine that have PAF-antagonistic properties and inhibit the development of atherosclerosis in animal models.
The regulatory role is thought to diverge from that point and be maintained as living organisms started to evolve.
PAF can be used as a local signaling molecule and travel over very short distances or it can be circulated throughout the body and act via endocrine.
The pathway to apoptosis can be inhibited by negative feedback from PAF acetylhydrolase (PAF-AH), an enzyme that catabolizes platelet-activating factor.
[9] Investigation led to the understanding that platelet and blood pressure response were dependent on the sn-2 propionyl analog.
PAF is produced by stimulated basophils, monocytes, polymorphonuclear neutrophils, platelets, and endothelial cells primarily through lipid remodeling.
The remodeling pathway is activated by inflammatory agents and it is thought to be the primary source of PAF under pathological conditions.
The fatty acid is removed from the sn-2 position of the three-carbon backbone of the phospholipid by phospholipase A2 (PLA2) to produce the intermediate lyso-PC (LPC).
Enzymes that are associated with the production of PAF are controlled by metal ions, thiol compounds, fatty acids, pH, compartmentalization, and phosphorylation and dephosphorylation.