Tjoelker L W, Wilder C, Eberhardt C, Stafforini D M, Dietsch G, Schimpf B, Hooper S, Le Trong H, Cousens L S, Zimmerman G A, Yamada Y, McIntyre T M, Prescott S M, Gray P W
ICOS Corporation, Bothell, Washington 98021, USA.
Nature. 1995 Apr 6;374(6522):549-53. doi: 10.1038/374549a0.
Platelet-activating factor (PAF) is a potent pro-inflammatory phospholipid that activates cells involved in inflammation. The biological activity of PAF depends on its structural features, namely an ether linkage at the sn-1 position and an acetate group at the sn-2 position. The actions of PAF are abolished by hydrolysis of the acetyl residue, a reaction catalysed by PAF acetylhydrolase. There are at least two forms of this enzyme--one intracellular and another that circulates in plasma and is likely to regulate inflammation. Here we report the molecular cloning and characterization of the human plasma PAF acetylhydrolase. The unique sequence contains a Gly-Xaa-Ser-Xaa-Gly motif commonly found in lipases. Recombinant PAF acetylhydrolase has the substrate specificity and lipoprotein association of the native enzyme, and blocks inflammation in vivo: it markedly decreases vascular leakage in pleurisy and paw oedema, suggesting that PAF acetylhydrolase might be a useful therapy for severe acute inflammation.
血小板活化因子（PAF）是一种强效促炎磷脂，可激活参与炎症反应的细胞。PAF的生物活性取决于其结构特征，即在sn-1位的醚键和sn-2位的乙酰基。PAF的作用可通过乙酰基残基的水解而消除，该反应由PAF乙酰水解酶催化。这种酶至少有两种形式——一种存在于细胞内，另一种在血浆中循环，可能参与调节炎症反应。在此，我们报告人血浆PAF乙酰水解酶的分子克隆及特性。其独特序列包含脂肪酶中常见的Gly-Xaa-Ser-Xaa-Gly基序。重组PAF乙酰水解酶具有天然酶的底物特异性和脂蛋白结合特性，并能在体内阻断炎症反应：它可显著减少胸膜炎时的血管渗漏和爪部水肿，提示PAF乙酰水解酶可能是治疗严重急性炎症的有效药物。
