Polymyxin B antagonizing biological activity of lipopolysaccharide.
- Author:
Yi-bin GUO
1
;
Li-ping CHEN
;
Hong-wei CAO
;
Ning WANG
;
Jiang ZHENG
;
Guang-xia XIAO
Author Information
- Publication Type:Journal Article
- MeSH: Animals; Cytokines; analysis; Limulus Test; Lipid A; antagonists & inhibitors; Lipopolysaccharides; antagonists & inhibitors; Macrophages; chemistry; Mice; Polymyxin B; pharmacology
- From: Chinese Journal of Traumatology 2007;10(3):180-183
- CountryChina
- Language:English
-
Abstract:
OBJECTIVETo investigate the mechanism of polymyxin B (PMB) antagonizing the biological activity of lipopolysaccharide (LPS).
METHODSThe affinity of PMB for LPS and lipid A was assayed by biosensor, and the neutralization of PMB for LPS (2 ng/ml) was detected by kinetic turbidimetric limulus test. The releases of TNF-alpha and IL-6 in murine peritoneal macrophages a (PMphi) after exposure to LPS (100 ng/ml) were detected, and the expression levels of TLR4, TNF-alpha and IL-6 mRNA in PMphi induced by LPS (100 ng/ml) were measured by RT-PCR.
RESULTSPMB had high-affinity to LPS and lipid A with dissociation equilibrium constants of 18.9 nmol/L and 11.1 nmol/L, respectively, and neutralized LPS in a dose-dependent manner. Furthermore, PMB could markedly inhibit the expressions of TLR4, TNF-alpha and IL-6 mRNA and the release of cycokines in LPS-stimulated murine peritoneal macrophages.
CONCLUSIONSPMB neutralizes LPS and inhibites the expression and release of cycokines in macrophages, in which the affinity of PMB for lipid A plays an important role.
