Chen Guoqian, Li Jianhua, Qiang Xiaoling, Czura Christopher J, Ochani Mahendar, Ochani Kanta, Ulloa Luis, Yang Huan, Tracey Kevin J, Wang Ping, Sama Andrew E, Wang Haichao
Department of Emergency Medicine, North Shore University Hospital, New York University School of Medicine, Manhasset, NY 11030, USA.
J Lipid Res. 2005 Apr;46(4):623-7. doi: 10.1194/jlr.C400018-JLR200. Epub 2005 Feb 1.
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.
硬脂酰溶血磷脂酰胆碱（LPC）最近被证明可通过刺激中性粒细胞通过依赖过氧化氢的机制消除入侵病原体，从而对致死性败血症起到保护作用。在此，我们证明硬脂酰LPC而非己酰LPC，通过抑制内毒素诱导的巨噬细胞/单核细胞释放HMGB1，可显著降低内毒素血症和败血症中循环高迁移率族蛋白B1（HMGB1）的水平。针对G2A（LPC的一种潜在细胞表面受体）的中和抗体部分消除了硬脂酰LPC介导的HMGB1释放抑制作用。因此，硬脂酰LPC对致死性实验性败血症的保护作用部分是通过促进入侵病原体的清除，部分是通过抑制内毒素诱导的晚期促炎细胞因子HMGB1的释放来实现的。
