Detection, characterisation and purification of a murine liver factor capable of desensitising towards the lethal activity of tumour necrosis factor.
Tumour necrosis factor (TNF) is a major mediator in septic shock and several inflammatory diseases such as hepatitis. Galactosamine (GalN) sensitises experimental animals for TNF and the combination TNF/GalN leads to a lethal inflammatory hepatitis. We describe that a single injection of lipopolysaccharide (LPS), interleukin-1 (IL-1) or TNF can desensitise against the lethality induced by TNF/GalN, but also against changes in metabolic parameters such as hypothermia and transaminase release, in a dose responsive way. We also describe the desensitising capacity of a component present in Mouse Liver Extract (MLE). The MLE desensitises mice against the effects of TNF/GalN in a dose responsive way. The activity of the MLE is heat labile and does not involve LPS, TNF, IL-1 or TNF soluble receptors. We describe partial and complete purification of the factor. Partially pure material protects mice against all changes induced by TNF/GalN. The protection is dose dependent and heat labile and also possible in endotoxin-hyporesponsive C3H/HeJ mice. The pure material protects against lethality, hypothermia and AST release and it appears as a heat labile protein of relative molecular weight of 70 kDa probably with a break down product of 35 kDa.
Wielockx
B
B
Department of Molecular Biology, VIB and University Ghent, Ledeganckstraat 35, 9000 Ghent, Belgium.
Hochepied
T
T
Staelens
J
J
Van Molle
W
W
Brouckaert
P
P
Libert
C
C
D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D003888:Desensitization, Immunologic; D004305:Dose-Response Relationship, Drug; D005260:Female; D005688:Galactosamine / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000633:toxicity; D007274:Injections, Intraperitoneal; D007375:Interleukin-1 / Q000008:administration & dosage* / Q000276:immunology; D008070:Lipopolysaccharides / Q000008:administration & dosage* / Q000276:immunology; D008099:Liver / Q000737:chemistry; D008110:Liver Extracts / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008970:Molecular Weight; D011506:Proteins / Q000276:immunology / Q000302:isolation & purification; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000633:toxicity
D007375:Interleukin-1; D008070:Lipopolysaccharides; D008110:Liver Extracts; D011506:Proteins; D014409:Tumor Necrosis Factor-alpha; D005688:Galactosamine; D001219:Aspartate Aminotransferases