J. Lipid Res. Neurobiology of Lipids (ISSN1683-5506)
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Originally published In Press as doi:10.1194/jlr.C400018-JLR200 on February 1, 2005

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Journal of Lipid Research, Vol. 46, 623-627, April 2005
Copyright © 2005 by American Society for Biochemistry and Molecular Biology

Rapid Communication

Suppression of HMGB1 release by stearoyl lysophosphatidylcholine:an additional mechanism for its therapeutic effects in experimental sepsis

Guoqian Chen*, Jianhua Li{dagger}, Xiaoling Qiang{dagger}, Christopher J. Czura{dagger}, Mahendar Ochani{dagger}, Kanta Ochani{dagger}, Luis Ulloa{dagger}, Huan Yang{dagger}, Kevin J. Tracey{dagger}, Ping Wang{dagger}, Andrew E. Sama* and Haichao Wang1,*,{dagger}

* Department of Emergency Medicine, North Shore University Hospital, New York University School of Medicine, Manhasset, NY 11030
{dagger} Center of Immunology and Inflammation, Institute for Medical Research at North Shore-LIJ, Manhasset, NY 11030

1 To whom correspondence should be addressed. e-mail: hwang{at}nshs.edu


ABSTRACT

Stearoyl lysophosphatidylcholine (LPC) has recently been proven protective against lethal sepsis by stimulating neutrophils to eliminate invading pathogens through an H2O2-dependent mechanism. Here, we demonstrate that stearoyl LPC, but not caproyl LPC, significantly attenuates circulating high-mobility group box 1 (HMGB1) levels in endotoxemia and sepsis by suppressing endotoxin-induced HMGB1 release from macrophages/monocytes. Neutralizing antibodies against G2A, a potential cell surface receptor for LPC, partially abrogated stearoyl LPC-mediated suppression of HMGB1 release.

Thus, stearoyl LPC confers protection against lethal experimental sepsis partly by facilitating the elimination of the invading pathogens and partly by inhibiting endotoxin-induced release of a late proinflammatory cytokine, HMGB1.

Abbreviations: HMGB1, high-mobility group box 1; LPC, lysophosphatidylcholine; LPS, lipopolysaccharide

Supplementary key words high-mobility group box 1 • endotoxemia • tumor necrosis factor • bacterial endotoxin


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