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. 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. It was discovered by French immunologist Jacques Benveniste in the early 1970s. PAF was the first phospholipid known to have messenger functions. Jacques Benveniste made significant contributions in the role and characteristics of PAF and its importance in inflammatory response and mediation. Using lab rats and mice, Jacques Benveniste 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. 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 (hardening of the arteries) can be attributed to PAF and PAF-like lipids and a diet with lipids that have antagonistic PAF properties can inhibit the development of heart disease. During the course of his studies, he also determined the chemical structure of the compound. The production of PAF can be found in the fossil records of protozoans, yeasts, plants, bacteria, and mammals. The oldest example of PAF being used in a regulatory role was found 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. PAF has been found in plants but its function has not yet been determined. The antifungal protein PAF from Penicillium chrysogenum exhibits growth-inhibitory activity against a broad range of filamentous fungi. Evidence suggests that disruption of Ca2+ signaling/homeostasis plays an important role in the mechanistic basis of PAF as a growth inhibitor. PAF also elicits hyperpolarization of the plasma membrane and the activation of ion channels, followed by an increase in reactive oxygen species in the cell and the induction of an apoptosis-like phenotype Cumulative evidence reveals that diabetes is a condition in which cell Ca2+ homeostasis is impaired. Defects in cell Ca2+ regulation were found in erythrocytes, cardiac muscle, platelets, skeletal muscle, kidney, aorta, adipocytes, liver, osteoblasts, arteries, lens, peripheral nerves, brain synaptosomes, retinal tissue, and pancreatic beta cells, confirming that this defect in cell Ca2+ metabolism is a basic pathology associated with the diabetic state.