Therapeutic effects of lysophosphatidylcholine in experimental sepsis.
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.
Yan
Ji-Jing
JJ
Department of Pharmacology, College of Medicine, Institute of Natural Medicine, Hallym University, 1 Okchon-dong, Chunchon, Gangwon-do, 200-702, South Korea.
Jung
Jun-Sub
JS
Lee
Jung-Eun
JE
Lee
Jongho
J
Huh
Sung-Oh
SO
Kim
Hee-Sung
HS
Jung
Kyeong Cheon
KC
Cho
Jae-Young
JY
Nam
Ju-Suk
JS
Suh
Hong-Won
HW
Kim
Yung-Hi
YH
Song
Dong-Keun
DK
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
D018797:Cell Cycle Proteins; D016207:Cytokines; C115270:G2A receptor; D008070:Lipopolysaccharides; D008244:Lysophosphatidylcholines; D043562:Receptors, G-Protein-Coupled