Induction of Lethality and Tolerance by Endotoxin Are Mediated by Macrophages through Tumor Necrosis Factor

Galanos, Chris; Freudenberg, Marina A.; Coumbos, A.; Matsuura, Motohiro; Lehmann, Volker; Bartholeyns, Jacques

doi:10.1159/000415883

Cited by 21 publications

(21 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, the production ofTNF-BP by the cells was prolonged and would imply that downregulation of a receptor for TNF also initiated new synthesis of receptor with continuous formation of TNF-BP. There is evidence for development of tolerance to the toxic effect of TNF after exposure to TNF itself (36,37), indicating that effects of TNF can be modulated by antagonistic mechanisms. One explanation could be the production ofTNF-BP.…”

Section: Discussionmentioning

confidence: 99%

Characterization in vitro of a human tumor necrosis factor-binding protein. A soluble form of a tumor necrosis factor receptor.

Lantz

Gullberg²,

Nilsson³

et al. 1990

J. Clin. Invest.

212

View full text Add to dashboard Cite

Tumor necrosis factor (TNF) is a pleiotropic mediator of inflammatory responses. A cysteine-rich, highly glycosylated 30-kD TNF-binding protein (TNF-BP) purified from urine may have a role in regulation because it protects in vitro against the biological effects of TNF. The cytotoxic effect of TNF on the fibrosarcoma cell line WEHI 164 was inhibited by-50% at a 10-fold excess of TNF-BP. The binding of TNF to the receptor was partially reversed after the addition of TNF-BP. Results from biosynthetic labeling of cells with 35S-cysteine followed by immunoprecipitation with anti-TNF-BP indicated that TNF-BP is formed and released at the cell surface by cleavage because no corresponding cellular polypeptide was observed. A cellular 60-kD polypeptide, which was immunoprecipitated with anti-TNF-BP, may correspond to the transmembrane TNF-receptor molecule and be the precursor of TNF-BP. Thus, TNF-BP appears to be a soluble form of a transmembrane TNF-receptor. Moreover our results demonstrate that the production of TNF-BP is increased when the TNF receptor is downregulated in cells by treatment with TNF or by activation of protein kinase C with phorbol esters. TNF-BP may be an important agent that blocks harmful effects of TNF, and, therefore, useful in clinical applications. (J. Clin.

show abstract

Section: Discussionmentioning

confidence: 99%

Characterization in vitro of a human tumor necrosis factor-binding protein. A soluble form of a tumor necrosis factor receptor.

Lantz

Gullberg²,

Nilsson³

et al. 1990

J. Clin. Invest.

212

View full text Add to dashboard Cite

show abstract

“…Induction of tolerance to in vivo toxicity of LPS as well as of TNF has been described [28]. For this reason the effect of incubation of Kupffer cells with LPS and TNF prior to exposure to cycloheximide and LPS or TNF was examined.…”

Section: Desensitization Of Kupffer Cells Towards the Lytic Action Ofmentioning

confidence: 99%

Interdependence of tumor necrosis factor, prostaglandin E₂, and protein synthesis in lipopolysaccharide‐exposed rat Kupffer cells

Peters

Karck

Decker

1990

European Journal of Biochemistry

View full text Add to dashboard Cite

Kupffer cells are the main producers of tumor necrosis factor‐α (TNF; cachectin) and eicosanoids in the liver exposed to lipopolysaccharide (endotoxin; LPS). A very rapid but transient release of TNF is followed by a slow, steady synthesis of prostaglandin E2 (PGE2). TNF itself is able to provoke eicosanoid synthesis in Kupffer cells; the rate and pattern of prostaglandin production are similar to those observed after treatment with LPS. Anti‐TNF antibodies completely neutralize TNF action on Kupffer cells, thus ruling out any participation of contaminating LPS. LPS stimulation of PGE2 production in Kupffer cells is reduced by the antiserum to 50%, indicating an involvement of TNF in the stimulatory action of LPS. On the other hand, PGE2, a potent inhibitor of LPS‐elicited TNF release, is able to suppress LPS‐ but not TNF‐stimulated eicosanoid synthesis in rat Kupffer cells. In addition to this autocrine circuit, extrahepatic factors participate in the regulation of Kupffer cell activation: glucocorticoids not only inhibit TNF or prostaglandin production, they also reverse the LPS‐specific changes in the prostaglandin pattern of Kupffer cells. LPS, TNF or cycloheximide when given alone in the concentration range applied in this study do not affect the viability of rat Kupffer cells. However, the combinations of cycloheximide and either LPS or TNF cause rapid death of the cultured cells. The cytolytic potential of either combination cannot be alleviated by treatment with glucocorticoids.

show abstract

“…3 Administration of uridine at the time of challenge also completely protected against lethality. It was further established, most definitively from adoptive transfer experiments, that in the D-galN model of LPS lethality, endotoxin responsive macrophages were essential, 1,2,[4][5][6] as is also recognized to be the case for LPS lethality in unsensitized mice. 7 While it is otherwise conceivable that D-galN might sensitize to lethality not only by increasing sensitivity to TNF but also by increasing TNF levels, D-galN does not, of itself, appreciably change circulating levels of TNF following challenge with LPS.…”

Section: Introductionmentioning

confidence: 99%

D-Galactosamine lethality model: scope and limitations

Silverstein¹

2004

J. Endotoxin Res.

106

View full text Add to dashboard Cite

D-Galactosamine (D-galN) is well established as sensitizing mice and other animals to the lethal effects of TNF, specifically, and by several orders of magnitude. Protection by anti-TNF neutralizing antibody is complete, as is (metabolically-based) protection by uridine. Sensitization occurs regardless of the origin of the released TNF, whether it is released from macrophages and/or T-cells. The same is true for the challenging agent which leads to the release of TNF, whether it is endotoxin, a superantigen, lipoprotein, bacterial DNA, or bacteria, either killed or proliferating. Most studies have utilized endotoxin as the challenging agent, and more than 70 agents have been reported to confer protection against LPS and/or TNF challenge in the model. The model has provided new insight regarding modes of protection, including from dexamethasone, which protects against challenge from LPS but not from challenge by TNF. The D-galN lethality model has also been used to test for synergistic behavior between different bacterial components, and to test for lethality when only small amounts of the challenging agent are available (lipid A chemistry).

show abstract

Induction of Lethality and Tolerance by Endotoxin Are Mediated by Macrophages through Tumor Necrosis Factor

Cited by 21 publications

References 0 publications

Characterization in vitro of a human tumor necrosis factor-binding protein. A soluble form of a tumor necrosis factor receptor.

Characterization in vitro of a human tumor necrosis factor-binding protein. A soluble form of a tumor necrosis factor receptor.

Interdependence of tumor necrosis factor, prostaglandin E₂, and protein synthesis in lipopolysaccharide‐exposed rat Kupffer cells

D-Galactosamine lethality model: scope and limitations

Contact Info

Product

Resources

About

Induction of Lethality and Tolerance by Endotoxin Are Mediated by Macrophages through Tumor Necrosis Factor

Cited by 21 publications

References 0 publications

Characterization in vitro of a human tumor necrosis factor-binding protein. A soluble form of a tumor necrosis factor receptor.

Characterization in vitro of a human tumor necrosis factor-binding protein. A soluble form of a tumor necrosis factor receptor.

Interdependence of tumor necrosis factor, prostaglandin E2, and protein synthesis in lipopolysaccharide‐exposed rat Kupffer cells

D-Galactosamine lethality model: scope and limitations

Contact Info

Product

Resources

About

Interdependence of tumor necrosis factor, prostaglandin E₂, and protein synthesis in lipopolysaccharide‐exposed rat Kupffer cells