title: Does high mobility group 1 protein function as a late mediator for LPS- or TNF-induced shock in galactosamine-sensitized mice?
abstract: The role of high mobility group-1 protein (HMG-1) in LPS- and TNF-alpha-induced lethal shock in galactosamine (GalN)-sensitized mice was investigated. No detectable HMG-1 levels were observed by immunoblotting analysis in plasma from untreated or GalN-sensitized BALB/c mice 5 h after LPS injection, although significant levels of HMG-1 were detected in plasma 6 h after the challenge. All GalN-sensitized BALB/c but not BALB/lps(d) mice succumbed by 6 h after LPS injection. When GalN-sensitized mice were injected with TNF-alpha, the presence of HMG-1 was seen at 5.5 h in plasma of BALB/c mice and at 6 h in BALB/lps(d) mice, although almost all GalN-sensitized BALB/c mice died by 6 h after challenge. The time-dependent phenomenon correlated with elevated serum aspartate aminotransferase (AST) levels and the appearance of apoptotic cells in livers. Administration of pooled plasma, equivalent to approximately 200 microg recombinant murine HMG-1, taken from mice on the verge of near death, did not result in induction of lethal shock in GalN-sensitized mice. Taken together with the late appearance of HMG-1 in moribund mice, these data suggest that HMG-1 does not decisively contribute to lethality in the GalN sensitization model.
authors.affiliation: Department of Biosciences, School of Science, Kitasato University, Sagamihara, Japan. hasunuma@jet.sci.kitasato-u.ac.jp
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Hasunuma
authors.forename: Hiroko
authors.initials: H
authors.lastname: Maruyama
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Takimoto
authors.forename: Roland
authors.initials: R
authors.lastname: Ryll
authors.forename: Shigenori
authors.initials: S
authors.lastname: Tanaka
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Kumazawa
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001219:Aspartate Aminotransferases / Q000097:blood; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D005688:Galactosamine / Q000633:toxicity*; D024243:HMGB1 Protein / Q000097:blood / Q000378:metabolism*; D006651:Histocytochemistry; D015151:Immunoblotting; D007700:Kinetics; D008070:Lipopolysaccharides / Q000633:toxicity*; D008099:Liver / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D011994:Recombinant Proteins / Q000633:toxicity; D012772:Shock, Septic / Q000097:blood / Q000139:chemically induced* / Q000401:mortality; D013047:Specific Pathogen-Free Organisms; D013534:Survival; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000633:toxicity*
chemical_list: D024243:HMGB1 Protein; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D005688:Galactosamine; D001219:Aspartate Aminotransferases