Induction of hepatocyte lipopolysaccharide binding protein in models of sepsis and the acute-phase response.
Lipopolysaccharide binding protein (LBP) is a serum glycoprotein that complexes with lipopolysaccharide (LPS) to facilitate macrophage response to endotoxin. To determine the conditions that stimulate LBP production in vivo, we measured the induction of LBP in models of inflammation produced by LPS, Corynebacterium parvum, and turpentine injection. Plasma aspartate aminotransferase and alanine aminotransferase concentrations and hepatocyte fibrinogen synthesis were elevated in all models. Northern blot analysis revealed 17-, 14-, and 20-fold upregulation of hepatocyte LBP mRNA following treatment with LPS, C parvum, and turpentine, respectively. Peritoneal macrophage interleukin 6 and tumor necrosis factor production following endotoxin stimulation was augmented by cultured hepatocyte supernatants, suggesting increased LBP synthesis in these groups. The results show that LBP mRNA is induced during hepatic inflammation and suggest that LBP is an acute-phase protein important in regulating the in vivo response to endotoxin.
Geller
D A
DA
Department of Surgery, University of Pittsburgh, Pa.
Kispert
P H
PH
Su
G L
GL
Wang
S C
SC
Di Silvio
M
M
Tweardy
D J
DJ
Billiar
T R
TR
Simmons
R L
RL
D000209:Acute-Phase Proteins; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D016470:Bacteremia / Q000097:blood / Q000276:immunology*; D001681:Biological Assay; D015152:Blotting, Northern; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000276:immunology; D004195:Disease Models, Animal; D004731:Endotoxins / Q000276:immunology; D005069:Evaluation Studies as Topic; D005340:Fibrinogen / Q000032:analysis; D007249:Inflammation; D015850:Interleukin-6 / Q000096:biosynthesis / Q000737:chemistry / Q000276:immunology; D008107:Liver Diseases / Q000097:blood / Q000276:immunology* / Q000473:pathology; D008264:Macrophages / Q000737:chemistry / Q000187:drug effects* / Q000276:immunology; D008297:Male; D008562:Membrane Glycoproteins; D010537:Peritoneum / Q000166:cytology; D015347:RNA Probes; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000737:chemistry / Q000276:immunology; D000099231:Lipopolysaccharide-Binding Protein
D000209:Acute-Phase Proteins; D000410:Alanine Transaminase; D001219:Aspartate Aminotransferases; D002352:Carrier Proteins; D004731:Endotoxins; D005340:Fibrinogen; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D015347:RNA Probes; D014409:Tumor Necrosis Factor-alpha; D000099231:Lipopolysaccharide-Binding Protein