Nature Medicine
10, 161 - 167 (2004)
Published online: 11 January 2004; | doi:10.1038/nm989
Therapeutic effects of lysophosphatidylcholine in experimental sepsisJi-Jing Yan1, 4, Jun-Sub Jung1, 4, Jung-Eun Lee1, 4, Jongho Lee1, 4, Sung-Oh Huh1, 3, 4, Hee-Sung Kim1, 3, Kyeong Cheon Jung2, Jae-Young Cho1, Ju-Suk Nam1, Hong-Won Suh1, Yung-Hi Kim1
& Dong-Keun Song1, 31
Department of Pharmacology, College of Medicine, Institute of Natural Medicine, Hallym University, 1 Okchon-dong, Chunchon, Gangwon-do, 200-702, South Korea
2
Department of Pathology, College of Medicine, Institute of Natural Medicine, Hallym University, 1 Okchon-dong, Chunchon, Gangwon-do, 200-702, South Korea
3
Biosynergen, Inc., 4th Floor, College of Medicine Bldg., Hallym University, 1 Okchon-dong, Chunchon, Gangwon-do, 200-702, South Korea
4
These authors contributed equally to this work.
Correspondence should be addressed to Dong-Keun Song dksong@hallym.ac.krSepsis 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 H2O2 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- (TNF-) from neutrophils. These results suggest that LPC can effectively prevent and treat sepsis and microbial infections.
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