ANTIINFLAMMATORY PROPERTIES OF A PLATELET-ACTIVATING-FACTOR ACETYLHYDROLASE

PLATELET-ACTIVATING factor (PAF) is a potent pro-inflammatory phosphol ipid that activates cells involved in inflammation(1,2). The biologica l 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 mole cular cloning and characterization of the human plasma PAF acetylhydro lase. The unique sequence contains a Gly-Xaa-Ser-Xaa-Gly motif commonl y found in lipases. Recombinant PAF acetylhydrolase has the substrate specificity and lipoprotein association of the native enzyme, and bloc ks inflammation in vivo: it markedly decreases vascular leakage in ple urisy and paw oedema, suggesting that PAF acetylhydrolase might be a u seful therapy for severe acute inflammation.