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ANTIINFLAMMATORY PROPERTIES OF A PLATELET-ACTIVATING-FACTOR ACETYLHYDROLASE
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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