Platelet-activating factor produced by endothelial cells. A molecule with autocrine and paracrine properties

Endothelial cells (EC) participate in microenvironment homeostasis by regulating the trafficking of cells and molecules from the bloodstream to the tissues. The 'area codes' used to control the trafficking are adhesion molecules, receptors which pick up external signals, and mediators of cell-to-cell communication. Platelet-activating factor (PAF) is a mediator that belongs to this class of 'area-code' molecules. PAF is an acetylated derivative of phosphatidylcholine which is produced by EC and may act in an autocrine manner. Several stimuli may induce the synthesis of PAF by EC with different time courses. Thrombin, elastase and tumor necrosis factor (TNF) are prototypic molecules inducing very-early, early and delayed PAF synthesis, respectively. These stimuli activate the 'remodelling pathway' which requires the activation of phospholipase A2 and acetyl CoA:1-alkyl-2-lyso-sn-glycero-3-phosphate acetyltransferase. The effects of very-early and early stimuli are mediated by a direct stimulation of this pathway, whereas the action of TNF is mediated by the new synthesis of a serine protease. Stimulated EC produce PAF molecules with both an ether and an ester bond at the sn-1 position, but the former is predominant. The PAF produced is partially exposed on the external membranes and participates in adhesion or migration of neutrophils. PAF released can also stimulate EC themselves, by interacting with a specific receptor. PAF stimulates the migration and the shape change of EC by activating calcium influx and several serine/threonine and tyrosine kinases which regulate the cytoskeleton.