title: Therapeutic effects of lysophosphatidylcholine in experimental sepsis.
abstract: 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.
authors.affiliation: Department of Pharmacology, College of Medicine, Institute of Natural Medicine, Hallym University, 1 Okchon-dong, Chunchon, Gangwon-do, 200-702, South Korea.
authors.forename: Ji-Jing
authors.initials: JJ
authors.lastname: Yan
authors.forename: Jun-Sub
authors.initials: JS
authors.lastname: Jung
authors.forename: Jung-Eun
authors.initials: JE
authors.lastname: Lee
authors.forename: Jongho
authors.initials: J
authors.lastname: Lee
authors.forename: Sung-Oh
authors.initials: SO
authors.lastname: Huh
authors.forename: Hee-Sung
authors.initials: HS
authors.lastname: Kim
authors.forename: Kyeong Cheon
authors.initials: KC
authors.lastname: Jung
authors.forename: Jae-Young
authors.initials: JY
authors.lastname: Cho
authors.forename: Ju-Suk
authors.initials: JS
authors.lastname: Nam
authors.forename: Hong-Won
authors.initials: HW
authors.lastname: Suh
authors.forename: Yung-Hi
authors.initials: YH
authors.lastname: Kim
authors.forename: Dong-Keun
authors.initials: DK
authors.lastname: Song
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000097:blood; D005260:Female; D006801:Humans; D008070:Lipopolysaccharides / Q000378:metabolism; D008244:Lysophosphatidylcholines / Q000378:metabolism / Q000627:therapeutic use*; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D018805:Sepsis / Q000188:drug therapy* / Q000401:mortality; D015996:Survival Rate
chemical_list: D018797:Cell Cycle Proteins; D016207:Cytokines; C115270:G2A receptor; D008070:Lipopolysaccharides; D008244:Lysophosphatidylcholines; D043562:Receptors, G-Protein-Coupled