CHARACTERIZATION OF THE PYROGENICITY OF TWO DIFFERENT LIPOPOLYSACCHARIDES AND THEIR LIPID A-BOVINE SERUM ALBUMIN COMPLEXES
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概要
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In order to elucidate the dependency of pyrogenicity of lipopolysaccharide (LPS) on the lipid A structure, we investigated the pyrogenicity of both LPS and lipid A prepared from Mima polymorpha var. oxidans which is deficient in 3-hydroxymyristic acids linked to the 3-hydroxy group of other fatty acids. LPS and lipid A were also prepared as reference compounds from Escherichia coli UKT-B. Furthermore, the establishment of reliable indices for pyrogenicity was undertaken. The following results were obtained. 1) The correlation in linearity was demonstrated between maximal increase in body temperature (ΔT_<max>) and dose of LPS or lipid A complexed with bovine serum albumin (BSA). The dose-response curves based on ΔT_<max> were more reliable statistically than the Fever Index-4h representing the area under fever curves for 4 h. 2) The minimum pyrogenic dose (MPD) of E. coli LPS was 1.6×10^<-3> μg/kg i.v. In contrast, the MPD of M. polymorpha LPS was 7.0×10^<-3> μg/kg i.v. By intracisternal injection, the MPD of E. coli LPS was 2.5×10^<-6> μg/kg and that of M. polymorpha LPS 1.0×10^<-4> μg/kg. 3) The end points of Limulus amoebocyte lysate gelation were 10^<-5> μg/ml in E. coli LPS and 10^<-3> μg/ml in M. polymorpha LPS. 4) The MPDs of lipid A/BSA complexes by i.v. injection were 0.15 μg/kg in E. coli and 2.5 μg/kg in M. polymorpha. 5) The rabbits immunized with E. coli lipid A/BSA complex acquired pyrogenic tolerance to the parent LPS but the cross tolerance to M. polymorpha LPS was not observed. These results indicated that certain differences in lipid A structure may be dominant factors for LPS-induced fever. However, it was suggested that the polysaccharide regions of a LPS molecule may also play an important role in LPS-induced fever.
- 公益社団法人日本薬学会の論文
著者
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OGAWA Yoshiyuki
Department of Hematology, National Hospital Organization Nishigunma National Hospital
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Ogawa Y
Setsunan Univ. Hirakata Jpn
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MURAI TOSHIMI
Department of Pharmacology and Bacteriology, National Institute of Hygienic Sciences, Osaka Branch
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KANOH SEIZABURO
Department of Pharmacology and Bacteriology, National Institute of Hygienic Sciences, Osaka Branch
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Murai T
National Inst. Hygienic Sciences Osaka Osaka Jpn
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Kanoh Seizaburo
Department Of Forensic Medicine Wakayama Prefectural Medical College
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Kanoh Seizaburo
Department Of Pharmacology And Bacteriology National Institute Of Hygienic Sciences Osaka Branch
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Ogawa Yoshiyuki
Department Of Bioengineering Nagaoka University Of Technology
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Murai Toshimi
Department Of Pharmacology And Bacteriology National Institute Of Hygienic Sciences Osaka Branch
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