Yan Ji-Jing, Jung Jun-Sub, Lee Jung-Eun, Lee Jongho, Huh Sung-Oh, Kim Hee-Sung, Jung Kyeong Cheon, Cho Jae-Young, Nam Ju-Suk, Suh Hong-Won, Kim Yung-Hi, Song Dong-Keun
Department of Pharmacology, College of Medicine, Institute of Natural Medicine, Hallym University, 1 Okchon-dong, Chunchon, Gangwon-do, 200-702, South Korea.
Nat Med. 2004 Feb;10(2):161-7. doi: 10.1038/nm989. Epub 2004 Jan 11.
Sepsis represents a major cause of death in intensive care units. Here we show that administration of lysophosphatidylcholine (LPC), an endogenous lysophospholipid, protected mice against lethality after cecal ligation and puncture (CLP) or intraperitoneal injection of Escherichia coli. In vivo treatment with LPC markedly enhanced clearance of intraperitoneal bacteria and blocked CLP-induced deactivation of neutrophils. In vitro, LPC increased bactericidal activity of neutrophils, but not macrophages, by enhancing H(2)O(2) production in neutrophils that ingested E. coli. Incubation with an antibody to the LPC receptor, G2A, inhibited LPC-induced protection from CLP lethality and inhibited the effects of LPC in neutrophils. G2A-specific antibody also blocked the inhibitory effects of LPC on certain actions of lipopolysaccharides (LPS), including lethality and the release of tumor necrosis factor-alpha (TNF-alpha) from neutrophils. These results suggest that LPC can effectively prevent and treat sepsis and microbial infections.
脓毒症是重症监护病房患者死亡的主要原因。在此我们表明，给予溶血磷脂酰胆碱（LPC），一种内源性溶血磷脂，可保护小鼠在盲肠结扎和穿刺（CLP）或腹腔注射大肠杆菌后免于死亡。LPC的体内治疗显著增强了腹腔细菌的清除，并阻止了CLP诱导的中性粒细胞失活。在体外，LPC通过增强吞噬大肠杆菌的中性粒细胞中H(2)O(2)的产生，增加了中性粒细胞而非巨噬细胞的杀菌活性。用LPC受体G2A的抗体孵育可抑制LPC诱导的对CLP致死性的保护作用，并抑制LPC在中性粒细胞中的作用。G2A特异性抗体也阻断了LPC对脂多糖（LPS）某些作用的抑制作用，包括致死性以及中性粒细胞中肿瘤坏死因子-α（TNF-α）的释放。这些结果表明，LPC可有效预防和治疗脓毒症及微生物感染。
