Human plasma platelet-activating factor acetylhydrolase. Association with lipoprotein particles and role in the degradation of platelet-activating factor.
Human plasma platelet-activating factor acetylhydrolase. Association with lipoprotein particles and role in the degradation of platelet-activating factor.
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DOI：
10.1016/s0021-9258(18)61335-3
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发表时间：
1987-03
期刊：
影响因子：
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通讯作者：
D. Stafforini;T. M. Mcintyre;M. E. Carter;S. Prescott
中科院分区：
文献类型：
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作者：
D. Stafforini;T. M. Mcintyre;M. E. Carter;S. Prescott
血小板活化因子（PAF）是一种由多种哺乳动物细胞合成的生物活性磷脂（1-O-烷基-2-乙酰基-sn-甘油-3-磷酸胆碱）。PAF诱导低血压，并激活中性粒细胞和血小板，以及其他作用。去除乙酰基部分消除了生物活性，因此该反应可以调节PAF的浓度及其生理效应。我们已经研究了这种反应的意义，它是在体外催化的乙酰水解酶存在于哺乳动物血浆，血细胞和组织。我们已经表明，血浆PAF-乙酰水解酶是负责PAF在整个人类血液中的降解和PAF降解的血浆或血细胞中的替代途径是可以忽略不计的。人血浆PAF-乙酰水解酶与低密度和高密度脂蛋白（LDL和HDL及apoE）相关。我们已经证实，活性是一个稳定的组成部分，这些颗粒的密度梯度超离心，肝素-琼脂糖层析，和免疫沉淀。LDL相关活性占离体血浆中发生的PAF降解的大部分或全部，而HDL相关活性对此过程贡献很小。然而，这两种活性可能是由于一种蛋白质，因为HDL和LDL相关的PAF-乙酰水解酶活性可以从一种脂蛋白转移到另一种脂蛋白。这些转移过程是pH依赖性和特异性的，因为它们仅发生在从LDL到HDL的一个充分表征的亚类（含apoE的HDL）之间，反之亦然。我们讨论了两个粒子之间的平衡和作用，这个过程可能在体内。
Platelet-activating factor (PAF) is a bioactive phospholipid (1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) synthesized by a variety of mammalian cell types. PAF induces hypotension, and activates neutrophils and platelets, among other actions. Removal of the acetyl moiety abolishes biological activity, so this reaction may regulate the concentration of PAF and its physiological effects. We have studied the significance of this reaction, which is catalyzed in vitro by an acetylhydrolase present in mammalian plasma, blood cells, and tissues. We have shown that the plasma PAF-acetylhydrolase is responsible for the degradation of PAF in whole human blood and that alternate pathways for PAF degradation in plasma or blood cells are negligible. Human plasma PAF-acetylhydrolase is associated with low and high density lipoproteins (LDL and HDL with apoE). We have confirmed that the activity is a stable component of these particles by density gradient ultracentrifugation, chromatography on heparin-agarose, and immunoprecipitation. The LDL-associated activity accounts for most or all of the PAF degradation that occurs in plasma ex vivo, while the HDL-associated activity contributes little to this process. However, the two activities likely are due to a single protein since the HDL- and LDL-associated PAF-acetylhydrolase activities can transfer from one lipoprotein to the other. These transfer processes are pH-dependent and specific, since they only occur from LDL to a well characterized subclass of HDL (apoE-containing HDL) and vice versa. We discuss the equilibrium between the two particles and the role that this process may have in vivo.