The Contribution of Individual Lipoproteins to the Degradation of Platelet-Activating Factor in Human Serum

Abstract

Platelet-activating factor (PAF) is rapidly degraded in vivo by the action of a specific acetylhydrolase. Measuring the PAF-acetylhydrolase activity in serum from 12 healthy volunteers a maximum velocity of 67.2 ± 11.8 nmol/min × ml and a K_m value of 15.8 ± 2.9 μmol/l were ascertained. More than 90% of the activity was found to be associated with lipoproteins. It was detected in isolated VLDL, LDL, Lp(a) as well as HDL₂ but not in HDL₃. The PAF-acetylhydrolase activities associated with the various lipoproteins were shown to behave like a unique enzyme with distinct kinetic properties. Because VLDL and LDL were found to take up about 5 and 2.5 times more PAF with respect to their mass than HDL, it is concluded that lipoproteins affect the PAF-acetylhydrolase activity at the level of substrate presentation. As a consequence of the distinct kinetic properties, the lipoprotein-associated PAF-acetylhydrolase activities do not contribute proportionately to the degradation of PAF in serum. The latter is shown to depend primarily on the amount of PAF-acetylhydrolase bound to the apoprotein B-containing lipoproteins.

PAF-acether-degrading acetylhydrolase in plasma LDL is inactivated by copper- and cell-mediated oxidation.

“…The K m of LDL-associated acetyihydrolase for PAF remained constant during oxidation and corresponded to that found earlier for both native LDL 28 and the enzyme purified from LDL. 23 From our kinetic studies, it is apparent that the acetyihydrolase conserved its affinity for PAF during oxidation of LDL; in contrast, its Vnu decreased progressively.…”

“…PAF is synthesized by various cells on activation, including monocytes, macrophages, endothelial cells, and platelets; such cells contribute to the development of atheromatous plaque. A fraction of the synthesized PAF is released from cells and transported in association with albumin 28 and plasma lipoproteins, including very-lowdensity lipoprotein, LDL, and high-density lipoprotein. 28 -32 PAF may be implicated in atherogenesis in different ways.…”

“…A fraction of the synthesized PAF is released from cells and transported in association with albumin 28 and plasma lipoproteins, including very-lowdensity lipoprotein, LDL, and high-density lipoprotein. 28 -32 PAF may be implicated in atherogenesis in different ways. First, as shown in vitro, membranebound PAF may act as an adhesion molecule between polymorphonuclear neutrophils and endothelial cells 33 or platelets, 34 and it may enhance vascular permeability in vivo.…”

Enhanced Degradation of Platelet-Activating Factor in Serum from Diabetic Patients

“…In previous studies [11] we demonstrated a close relationship between the concentrations of lipids and apolipoproteins in plasma and the capacity to degrade PAF. Moreover, there is evidence that the lipoproteins exert a regulatory func tion onto the degradation of PAF [12]. Therefore, the present study was undertaken to investigate whether there is any difference in the degradation of PAF in serum from diabetic patients which is characterized fre quently by an abnormal lipoprotein profile.…”

Letters to the Editor

“…I wish to comment on two articles on pafacether published in the May/June issue of Haemostasis, by Ostermann et al [1] and by Hofmann et al [2]. These papers are remark able in that the reference lists comprise about 99% American references.…”