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| ANTIINFLAMMATORY PROPERTIES OF A PLATELET-ACTIVATING-FACTOR ACETYLHYDROLASE |
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| Author(s): TJOELKER LW, WILDER C, EBERHARDT C, STAFFORINI DM, DIETSCH G, SCHIMPF B, HOOPER S, LETRONG H, COUSENS LS, ZIMMERMAN GA, YAMADA Y, MCINTYRE TM, PRESCOTT SM, GRAY PW |
| Source: NATURE Volume: 374 Issue: 6522 Pages: 549-553 Published: APR 6 1995 |
| Times Cited: 332 References: 27 |
| Abstract: 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. |
| Document Type: Article |
| Language: English |
Addresses:
1. UNIV UTAH, ECCLES INST HUMAN GENET, PROGRAM HUMAN MOLEC BIOL & GENET, SALT LAKE CITY, UT 84112 USA 2. UNIV UTAH, INST CARDIOVASC RES & TRAINING, SALT LAKE CITY, UT 84112 USA 3. ICOS CORP, BOTHELL, WA 98021 USA |
| Publisher: MACMILLAN MAGAZINES LTD, 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF |
| Subject Category: Multidisciplinary Sciences |
| IDS Number: QR069 |
| ISSN: 0028-0836 |
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