Inactivation of platelet-activating factor in plasma
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. Preincu...
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Published in | Blood & Vessel Vol. 17; no. 2; pp. 158 - 160 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
The Japanese Society on Thrombosis and Hemostasis
1986
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Abstract | 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. |
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AbstractList | 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. |
Author | OSANAI, Ikuko KAWAMURA, Yoko SATOH, Kei TAKAMATSU, Mutsu TAKAMATSU, Shigeru MIZUNO, Seitoku |
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References | 2) Hanahan, D. J., Demopoulos, C. A., Liehr, J., Pinckard, R. N.: Identification of platelet activating factor isolated from rabbit basophils as acetyl glyceryl ether phosphorylcholine. J. Biol. Chem., 255; 5514-5516, 1980. 4) Born, G. V. R.: Aggregation of blood platelets by adenosine diphosphate and its reversal. Nature, 195; 927-929, 1962. 1) Prescott, S. M., Zimmerman, G. A., McIntyre, T. M.: Human endothelial cells in culture produce platelet-activating factor (1-alkyl-2-acetyl-sn-glycero-3-phosphocholine) when stimulated with thrombin. Proc. Natl. Acad. Sci. USA, 81; 3534-3538, 1984. 5) Havel, R. J., Eder, H. A., Bragdon, J. H.: Distribution and chemical composition of ultracentrifugally separated lipoproteins in human serum. J. Clin. Invest., 34; 1345-1353, 1955. 3) Blank, M. L., Lee, T., Fitzgerald, V., Snyder, F.: A specific acetylhydrolase for 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine (a hypotensive and platelet activating lipid). J. Biol. Chem., 256; 175-178, 1981. |
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SubjectTerms | acetylhydrolase diisopropylfluorophosphate plasma lipoproteins platelet aggregation platelet-activating factor (PAF) |
Title | Inactivation of platelet-activating factor in plasma |
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