A role for PAF-acether (platelet-activating factor) in platelet-dependent vascular diseases?
Platelets-isolated or in conjunction with leukocytes-interact with vessel walls in many experimental and human diseases. Several mediators are held responsible for platelet activation and interaction with leukocytes, among which PAF-acether (platelet-activating factor) is a prime candidate. This phospholipid mediator is released by most inflammatory cells, including neutrophils, by isolated organs such as kidney and heart, is a potent platelet and neutrophil agonist, and exerts major vasoactive properties. Its biosynthesis involves a two-step enzymatic process yielding the active molecule from the membrane alkyl-ether choline-containing phospholipids. The first step implicates a phospholipase A2 that hydrolyzes a long-chain fatty acid (which can be arachidonic acid) from membrane phospholipids, leaving the intermediate compound lyso PAF-acether, a PAF-acether precursor that is acetylated by an acetyltransferase in a second step. It can also result from deacetylation of PAF-acether by an acetylhydrolase. PAF-acether release might explain the intervention of platelets in diseases such as glomerulonephritis and allergic vasculitis, in which the involvement of neutrophils and platelets is frequently noted. The end result of these complex sets of cell-to-cell interactions is the release of most known inflammatory mediators, influencing vascular permeability, cell infiltration, and smooth muscle contraction. Nevertheless, direct evidence for the implication of these rather well-defined cellular and molecular interactions in human pathologic states remains to be obtained.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D000001:Calcimycin / Q000494:pharmacology; D006801:Humans; D006967:Hypersensitivity / Q000097:blood; D007674:Kidney Diseases / Q000097:blood; D010972:Platelet Activating Factor / Q000502:physiology*; D011817:Rabbits; D014652:Vascular Diseases / Q000503:physiopathology*
D001095:Arachidonic Acids; D010972:Platelet Activating Factor; D016718:Arachidonic Acid; D000001:Calcimycin