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J. Lipid Res.
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A more recent version of this article appeared on August 1, 2008

Papers In Press, published online ahead of print May 5, 2008
J. Lipid Res., doi:10.1194/jlr.M700446-JLR200
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Submitted on October 9, 2007
Revised on April 14, 2008
Accepted on May 4, 2008

The effect of lipid bound apoA-I cysteine mutants on lipopolysaccharide induced endotoxemia in mice

Yunlong Wang, Xuewei Zhu, Gang Wu, Le Shen, and Baosheng Chen

Biochemistry and Molecular Biology, National Laboratory of Medical Molecular Biology,Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005

Corresponding Author: bschen{at}ibms.pumc.edu.cn

High density lipoprotein (HDL) has been shown able to neutralize the toxicity of the lipopolysaccharide (LPS). Our previous study (J Lipid Res. 2005; 46: 1303-1311) characterized the prosperities of secondary structure and in vitro functions of different cysteine mutants of apolipoprotein A-I (apoA-I). Here we reconstituted recombinant HDLs (named as rHDLwt, rHDL52, rHDL 74, rHDL107, rHDL129, rHDL173, rHDL195 and rHDL228) by mixing wild type (WT) or those mutants with dipalmitoyl phosphatidylcholine (DPPC) and examined their in vivo effects on LPS induced endotoxemia in mice. Our results showed that after 24h injection, mice receiving rHDL 74 or rHDL52 had a significant decrease of plasma tumor necrosis factor  (TNF-) and interleukin-1(IL-1) compared with control mice either receiving saline or rHDLwt ( P<0.05). Administration of rHDL74 to mice infected with LPS also led to a decrease of plasma interleukin-6 (IL-6), protection of lung against acute injury, and attenuation of endotoxin-induced clinical symptoms in mice compared with controls only injected with LPS. However, injection of rHDL228 significantly increased plasma concentration of TNF- and exacerbate LPS induced lung injury. In summary, compared with rHDLwt, rHDL74 and rHDL52 exhibit higher capabilities of anti-inflammation; whereas rHDL228 shows hyper-proinflammation by exacerbating LPS induced endotoxemia in mice.


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J. Lipid Res., August 1, 2008; 49(8): 1605 - 1606.
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