Platelet-activating factor

Platelet-activating factor, also known as a PAF, PAF-acether or AGEPC (acetyl-glyceryl-ether-phosphorylcholine) is a potent phospholipid activator and mediator of many leukocyte functions, including 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.

It is produced in response to specific stimuli by a variety of cell types, including neutrophils, basophils, injured tissue, monocytes/macrophages, platelets, and endothelial cells.

Chemistry
Several molecular species of platelet-activating factor that vary in the length of the O-alkyl side-chain have been identified.


 * Its alkyl group is connected by an ether linkage at the C1 carbon to a 16-carbon chain.
 * The acyl group at the C2 carbon is an acetate unit (as opposed to a fatty acid) whose short length increases the solubility of PAF, allowing it to function as a soluble signal messenger.
 * The C3 has a phosphocholine head group, just like standard phosphatidylcholine.

Function
It is an important mediator of bronchoconstriction.

It causes platelets to aggregate and blood vessels to dilate. Thus, it is important to the process of hemostasis. At a concentration of 10-12 mol/L, PAF causes life threatening inflammation of the airways to induce asthma like symptoms.

Toxins such as fragments of destroyed bacteria induce the synthesis of PAF, which causes a drop in blood pressure and reduced volume of blood pumped by the heart, which leads to shock and possibly death.

History
It was discovered by French immunologist Jacques Benveniste in the early 1970s. Its structure was elucidated by Constantinos A. Demopoulos in 1979.

Biosynthesis and degradation
PAF is biosynthesized from lysophosphatidylcholine (LPC) and acetyl CoA by the enzyme LPC acetyltransferase (LPCAT).

It is degraded (thereby terminating its capacity to act as a signaling molecule) by a group of enzymes called PAF acetylhydrolases (PAFAHs), which are related to phospholipase A2.

Antagonists

 * SM-12502 is a PAF antagonist, which is metabolized in the liver by the enzyme CYP2A6.
 * Rupatadine is an antihistamine and PAF antagonist used to treat allergies.