1986 Volume 17 Issue 2 Pages 158-160
Platelet aggregation induced by platelet-activating factor (PAF) was inhibited by the prior incubation of PAF solution with citrated human plasma. Such neutralization by plasma of PAF was found to be dependent on the amount of plasma preincubated with PAF and on the period of the incubation. Preincubation of ADP solution with plasma did not affect its platelet aggregating activity. PAF-neutralizing activity was abolished by the pretreatment of plasma with diisopropylfluorophosphate (DFP) in a dose-dependent manner, and a complete inhibition was observed with 5mM DFP. Plasma lipoprotein fraction, prepared by ultracentrifugation, was found to account for the inactivation of PAF by plasma, and lipoprotein-deficient plasma was virtually inactive.
PAF, identified as 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine, is known to be metabolized by a specific enzyme called acetylhydrolase which hydrolyzes the acetyl moiety at the sn-2 position of the molecule. This enzyme has been found in various tissues as well as in plasma. The dose-dependent inhibition by DFP implies that acetylhydrolase is solely responsible for the inactivation of PAF by plasma and that the hydroxy group of a serine residue plays an important role as the active site of this enzyme. The result showing the association of PAF-neutralizing activity with plasma lipoproteins may suggest the existence of a unknown mechanism involved in the interaction between platelets and lipoproteins.
