Suppression of HMGB1 release by stearoyl lysophosphatidylcholine:an additional mechanism for its therapeutic effects in experimental sepsis.
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.
Chen
Guoqian
G
Department of Emergency Medicine, North Shore University Hospital, New York University School of Medicine, Manhasset, NY 11030, USA.
Li
Jianhua
J
Qiang
Xiaoling
X
Czura
Christopher J
CJ
Ochani
Mahendar
M
Ochani
Kanta
K
Ulloa
Luis
L
Yang
Huan
H
Tracey
Kevin J
KJ
Wang
Ping
P
Sama
Andrew E
AE
Wang
Haichao
H
D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004731:Endotoxins / Q000494:pharmacology; D024243:HMGB1 Protein / Q000378:metabolism*; D008244:Lysophosphatidylcholines / Q000494:pharmacology* / Q000627:therapeutic use*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D021381:Protein Transport; D018805:Sepsis / Q000188:drug therapy* / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D004731:Endotoxins; D024243:HMGB1 Protein; D008244:Lysophosphatidylcholines; D014409:Tumor Necrosis Factor-alpha; C026564:stearoyl alpha-lysolecithin