High mortality rate of (NZW x BXSB)F1 mice induced by administration of lipopolysaccharide attributes to high production of tumour necrosis factor-alpha by increased numbers of dendritic cells.
(NZW x BXSB)F1 mice (W/BF1 mice) have been reported to be a type of autoimmune-prone mice, showing symptoms of proteinuria, anti-DNA antibodies and anti-platelet antibodies. In this paper, we report that W/BF1 mice show hyperproduction of tumour necrosis factor (TNF)-alpha, responding to lipopolysaccharide (LPS) in comparison with normal mice, resulting in induction of death. In normal mice, monocytes/macrophages (Mo/MØ) are the main producer of TNF-alpha, while both Mo/MØ and dendritic cells (DCs) produce TNF-alpha in W/BF1 mice. Because the number of DCs is higher in W/BF1 mice, the main producers of TNF-alpha in W/BF1 mice are thought to be DCs. Moreover, administration of anti-TNF-alpha antibodies rescued the W/BF1 mice from death induced by LPS, suggesting that TNF-alpha is crucial for the effect of LPS. Although there is no significant difference in the expression of Toll-like receptor-4 (TLR-4) on DCs between B6 and W/BF1 mice, nuclear factor kappa b activity of DCs from W/BF1 mice is augmented under stimulation of LPS in comparison with that of normal mice. These results suggest that the signal transduction from TLR-4 is augmented in W/BF1 mice in comparison with normal mice, resulting in the hyperproduction of TNF-alpha and reduced survival rate. The results also suggest that not only the quantity of endotoxin, but also the host conditions, the facility to translate signal from TLR, and so on, could reflect the degree of bacterial infections and prognosis.
Koike-Kiriyama
N
N
First Department of Pathology, Kansai Medical University, Moriguchi City, Osaka, Japan.
Adachi
Y
Y
Iwasaki
M
M
Amou
Y
Y
Shigematsu
A
A
Koike
Y
Y
Minamino
K
K
Mukaide
H
H
Shi
M
M
Yanai
S
S
Matsumura
M
M
Ikehara
S
S
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D008070:Lipopolysaccharides / Q000276:immunology / Q000633:toxicity*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D015398:Signal Transduction / Q000276:immunology; D013154:Spleen / Q000276:immunology; D016019:Survival Analysis; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000276:immunology
D008070:Lipopolysaccharides; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha
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