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Polymyxin B antagonizing biological activity of lipopolysaccharide
作者姓名:郭毅斌  陈莉萍  曹红卫  王宁  郑江  肖光夏
作者单位:[1]Medical Research Center, Southwest Hospital, Third Military Medical University, Chongqing 400038, China [2]Institute of Hepatobiliary Surgery of PLA, Southwest Hospital, Third Military Medical University, Chongqing400038, China [3]Bum Research Institute, Southwest Hospital, Third Military Medical University, Chongqing 400038, China
基金项目:This work was supported by the grant from the National Key Technologies R&D Program (G1999054203).
摘    要:Objective : To investigate the mechanism of polymyxin B ( PMB ) antagonizing the biological activity of Hipopolysaccharide (LPS). Methods: The 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 limnins test. The releases of TNF-α and IL-6 in murine peritoneal macrophages (PMφ) after exposure to LPS ( 100 ng/ml) were detected, and the expression levels of TLR4, TNF-α and IL-6 mRNA in PMφ induced by LPS (100 ng/ml) were measured by RT-PCR. Results: PMB 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 dosedependent manner. Furthermore, PMB could markedly inhibit the expressions of TLR4, TNF-α and IL-6 mRNA and the release of cycokines in LPS-stimniated murine PMφ. Conclusions: PMB 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.

关 键 词:多粘菌素B  脂多糖  生物学活性  拮抗作用  中和作用
收稿时间:2006-06-12

Polymyxin B antagonizing biological activity of lipopolysaccharide
GUO Yi-bin,CHEN Li-ping,CAO Hong-wei,WANG Ning,ZHENG Jiang,XIAO Guang-xia.Polymyxin B antagonizing biological activity of lipopolysaccharide[J].Chinese Journal of Traumatology(English Edition),2007,10(3):180-183.
Authors:GUO Yi-bin  CHEN Li-ping  CAO Hong-wei  WANG Ning  ZHENG Jiang  XIAO Guang-xia
Institution:1. Medical Research Center, Southwest Hospital, Third Military Medical University, Chongqing 400038, China
2. Institute of Hepatobiliary Surgery of PLA, Southwest Hospital, Third Military Medical University, Chongqing 400038, China
3. Burn Research Institute, Southwest Hospital, Third Military Medical University, Chongqing 400038, China
Abstract:OBJECTIVE: To investigate the mechanism of polymyxin B (PMB) antagonizing the biological activity of lipopolysaccharide (LPS). METHODS: The 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. RESULTS: PMB 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. CONCLUSIONS: PMB 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.
Keywords:Polymyxin B  Lipopolysaccharides  Macrophages  Biosensing techniques
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