ANTIINFLAMMATORY PROPERTIES OF A PLATELET-ACTIVATING-FACTOR ACETYLHYDROLASE
ANTIINFLAMMATORY PROPERTIES OF A PLATELET-ACTIVATING-FACTOR ACETYLHYDROLASE
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DOI：
10.1038/374549a0
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发表时间：
1995-04-06
期刊：
影响因子：
64.8
通讯作者：
GRAY, PW
中科院分区：
文献类型：
--
作者：
TJOELKER, LW;WILDER, C;GRAY, PW
血小板激活因子(PAF)是一种有效的促炎磷脂，能激活参与炎症的细胞(1，2)。PAF的生物活性取决于其结构特征，即在sn-1位有一个醚键，在sn-2位有一个乙酸基。PAF的作用通过乙酰基残基的水解而取消，该反应是由PAF乙酰水解酶催化的。这种酶至少有两种形式--一种在细胞内，另一种在血浆中循环，可能调节炎症。在这里，我们报道了人血浆PAF乙酰水解酶的分子克隆和特性。该独特的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专一性和脂蛋白结合能力，可阻断体内炎症反应：它能显著减少胸膜炎和足肿胀时的血管渗漏，提示PAF乙酰水解酶可能是治疗严重急性炎症的有效药物。
PLATELET-ACTIVATING factor (PAF) is a potent pro-inflammatory phospholipid that activates cells involved in inflammation(1,2). 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.