Platelet-activating factor--a powerful lipid autacoid possibly involved in microangiopathy

Microvascular injury includes diffuse endothelial and periendothelial damage and increased leukocyte/platelet-endothelium interactions including cell adhesion and liberation of powerful autacoids, growth and coagulation factors, all capable of causing vessel wall injury. Platelet-activating factor (PAF) is an ether-lipid mediator of inflammation, produced by and active on both platelets and endothelial cells (EC) at nanomolar concentrations. Its structure, biosynthesis and origin as well as some regulatory properties of the related enzymes are considered. The in vivo effects of PAF, as well as its action on selected cell types, such as platelets, neutrophils and EC, are briefly reviewed. PAF production may explain the intervention of platelets and neutrophils as well as increased vascular permeability in kidney, lung and retinal diseases. Pharmacological modulation of PAF production and activity is discussed with particular attention to the inhibitory effect of calcium dobesilate, a drug used in human diabetic retinopathy, on PAF production from the human endothelial cell line EA926.