The Essential Role of the Liver in Detoxification of Endotoxin

Farrar, W. Edmund; Corwin, Laurence M.

doi:10.1111/j.1749-6632.1966.tb52397.x

Cited by 51 publications

(22 citation statements)

References 26 publications

(6 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Evidence supporting our suggestion that endotoxin is detoxified in the liver by oxidation of its fatty ,acids by mitochondria is presented in detail in previous papers (7,8,11) .…”

supporting

confidence: 62%

Susceptibility of Rabbits to Pyrogenic and Lethal Effects of Endotoxin after Acute Liver Injury

Farrar

Eidson

Kent

1968

Experimental Biology and Medicine

View full text Add to dashboard Cite

“…Evidence supporting our suggestion that endotoxin is detoxified in the liver by oxidation of its fatty ,acids by mitochondria is presented in detail in previous papers (7,8,11) .…”

supporting

confidence: 62%

Susceptibility of Rabbits to Pyrogenic and Lethal Effects of Endotoxin after Acute Liver Injury

Farrar

Eidson

Kent

1968

Experimental Biology and Medicine

View full text Add to dashboard Cite

“…The end point of nitrogen metabolism is the cytotoxic compound ammonia. The urea cycle in hepatocytes converts ammonia to urea [43]. Low levels of urea and albumin secretion were detected in undifferentiated hESCs and differentiated adherent cells (Fig.…”

Section: Maturation Of Spheroid Cells Into Hepatocyte-like Cellsmentioning

confidence: 92%

Engraftment Potential of Spheroid-Forming Hepatic Endoderm Derived from Human Embryonic Stem Cells

Kim

Woo

et al. 2013

Stem Cells and Development

View full text Add to dashboard Cite

Transplantation and drug discovery programs for liver diseases are hampered by the shortage of donor tissue. While recent studies have shown that hepatic cells can be derived from human embryonic stem cells (hESCs), few cases have shown selective enrichment of hESC-derived hepatocytes and their integration into host liver tissues. Here we demonstrate that the dissociation and reaggregation procedure after an endodermal differentiation of hESC produces spheroids mainly consisted of cells showing hepatic phenotypes in vitro and in vivo. A combined treatment with Wnt3a and bone morphogenic protein 4 efficiently differentiated hESCs into definitive endoderm in an adherent culture. Dissociation followed by reaggregation of these cells in a nonadherent condition lead to the isolation of spheroid-forming cells that preferentially expressed early hepatic markers from the adherent cell population. Further differentiation of these spheroid cells in the presence of the hepatocyte growth factor, oncostatin M, and dexamethasone produced a highly enriched population of cells exhibiting characteristics of early hepatocytes, including glycogen storage, indocyanine green uptake, and synthesis of urea and albumin. Furthermore, we show that grafted spheroid cells express hepatic features and attenuate the serum aspartate aminotransferase level in a model of acute liver injury. These data suggest that hepatic progenitor cells can be enriched by the spheroid formation of differentiating hESCs and that these cells have engraftment potential to replace damaged liver tissues.

show abstract

“…Previous attempts to identify a hepatic mechanism for inactivating endotoxin have been unsuccessful (4,10,39). In retrospect, two factors may have contributed to this difficulty: the relatively slow rate with which enzymatic deacylation of LPS proceeds in vivo and the fact that its impact on the liver becomes apparent several days after the initial inflammatory response has subsided.…”

Section: Discussionmentioning

confidence: 99%

A Host Lipase Detoxifies Bacterial Lipopolysaccharides in the Liver and Spleen

Shao¹,

Lu²,

Katz

et al. 2007

Journal of Biological Chemistry

121

View full text Add to dashboard Cite

Much of the inflammatory response of the body to bloodborne Gram-negative bacteria occurs in the liver and spleen, the major organs that remove these bacteria and their lipopolysaccharide (LPS, endotoxin) from the bloodstream. We show here that LPS undergoes deacylation in the liver and spleen by acyloxyacyl hydrolase (AOAH), an endogenous lipase that selectively removes the secondary fatty acyl chains that are required for LPS recognition by its mammalian signaling receptor, MD-2-TLR4. We further show that Kupffer cells produce AOAH and are required for hepatic LPS deacylation in vivo. AOAH-deficient mice did not deacylate LPS and, whereas their inflammatory responses to low doses of LPS were similar to those of wild type mice for ϳ3 days after LPS challenge, they subsequently developed pronounced hepatosplenomegaly. Providing recombinant AOAH restored LPS deacylating ability to Aoah ؊/؊ mice and prevented LPS-induced hepatomegaly. AOAH-mediated deacylation is a previously unappreciated mechanism that prevents prolonged inflammatory reactions to Gram-negative bacteria and LPS in the liver and spleen.

show abstract

The Essential Role of the Liver in Detoxification of Endotoxin

Cited by 51 publications

References 26 publications

Susceptibility of Rabbits to Pyrogenic and Lethal Effects of Endotoxin after Acute Liver Injury

Susceptibility of Rabbits to Pyrogenic and Lethal Effects of Endotoxin after Acute Liver Injury

Engraftment Potential of Spheroid-Forming Hepatic Endoderm Derived from Human Embryonic Stem Cells

A Host Lipase Detoxifies Bacterial Lipopolysaccharides in the Liver and Spleen

Contact Info

Product

Resources

About