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Platelet-activating factor

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Platelet-activating factor

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.

PAF is produced by a variety of cells, but especially those involved in host defense, such as platelets, endothelial cells, neutrophils, monocytes, and macrophages. PAF is continuously produced by these cells but in low quantities and production is controlled by the activity of PAF acetylhydrolases. It is produced in larger quantities by inflammatory cells in response to specific stimuli.

PAF was discovered by French immunologist Jacques Benveniste in the early 1970s. PAF was the first phospholipid known to have messenger functions. 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. These developments led to the finding that macrophages produce PAF and that macrophages play an important function in aggregation of platelets and liberation of their inflammatory and vasoactive substances.[citation needed]

Further studies on PAF were conducted by Constantinos A. Demopoulos in 1979. Demopoulos found that PAF plays a crucial role in heart disease and strokes. 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. During the course of his studies, he also determined the chemical structure of the compound.

PAF can be found in protozoans, yeasts, plants, bacteria, and mammals. PAF has regulatory role in protozoans. The regulatory role is thought to diverge from that point and be maintained as living organisms started to evolve. During evolution, functions of PAF in the cell have been changing and enlarging.[citation needed]

PAF has been found in plants but its function has not yet been determined.[citation needed]

PAF is used to transmit signals between neighboring cells and acts as a hormone, cytokines, and other signaling molecules. The PAF signaling system can trigger inflammatory and thrombotic cascades, amplify these cascades when acting with other mediators, and mediate molecular and cellular interactions (cross talk) between inflammation and thrombosis. Unregulated PAF signaling can cause pathological inflammation and has been found to be a cause in sepsis, shock, and traumatic injury. 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.

PAF initiates an inflammatory response in allergic reactions. This has been demonstrated in the skin of humans and in the paws and skin of lab rabbits and rodents. The inflammatory response is enhanced by the use of vasodilators, including prostaglandin E1 (PGE,) and PGE2 and inhibited by vasoconstrictors.

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