D-Galactosamine Ire atotoxicit Is Associated With Endotoxin Sensitivity and Mediated by Lymphoreticular Cells in Mice

doi:10.1016/S0016-5085(85)80142-6

Gastroenterology

Volume 88, Issue 1, Part 1, January 1985, Pages 115-121

https://doi.org/10.1016/S0016-5085(85)80142-6 Get rights and content

Two strains of mice (C57BL/10ScN and C3H/HeJ) that carry the same mutant lipopolysaccharide gene (Lps^d) which makes them resistant to the toxic effects of endotoxin (LPS) are also partially resistant to the hepatotoxic effects of D-galactosamine. As measured by serum alanine aminotrans f erase, the degree of liver injury induced by D-galactosamine ih the LPS-resistant strains is only 10%–30% that of closely related strains of LPS-sensitive mice. Similarly, histopathologic changes are less pronounced in the endotoxin-resistant strains than in LPS-susceptible mice. By transferring spleen cells from LPS-susceptible strains to lethally irradiated, LPS-resistant mice, we established that susceptibility to D-galactosamine is mediated by lymphoreticular cells. Radiation-resistant spleen cells transferred D-galactosamine sensitivity, suggesting a role for macrophages. We did not exclude the possibility that lymphocytes can also transfer the response to D-galactosamine. These results establish that in mice, D-galactosamine sensitivity is associated with endotoxin sensitivity and that the former is mediated by lymphoreticular cells, not by hepatocytes.

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Taken collectively, these observations suggest that LECT2 has an inhibitory effect on SEA/d-GalN-induced lethal reactions. To assess the severity of tissue damage, we examined the histopathological findings of not only the liver tissue, in which d-GalN is known to sensitize the cells to TNF-α-induced apoptosis [26,27], but also the lung tissue of B6 and LECT2−/− mice treated with SEA/d-GalN. As depicted in Fig. 2, the liver showed massive intra-hepatic hemorrhage in the B6 mice at 24 and 48 h after treatment with 1.0 μg SEA/d-GalN, whereas the livers of 0.1 μg SEA/d-GalN-treated mice appeared almost intact at the corresponding times.
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⁺: This study was supported by the Research Service, Veterans Administration.

⁺⁺: The authors thank Dr. John Ryan for providing the phenol-water extracted lipopolysaccharide and Janeen McCracken and Tammy Shaffer for skillful preparation of the manuscript.

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D-Galactosamine Ire atotoxicit Is Associated With Endotoxin Sensitivity and Mediated by Lymphoreticular Cells in Mice+,++

J Biol Chem

Gastroenterology

Gasteroenterology

Gastroenterology

Gastroenterology

Gastroenterology

Gastroenterology

Cell Immunol

Galactosamine induced liver injury

Cell damage by trapping of biosynthetic intermediates

Hoppe Seyler's Z Physiol Chem

Endotoxin, reticuloendothelial function, and liver injury

Hepatology

Significance of endotoxemia in experimental “galactosamine-hepatitis” in the rat

Acta Hepato-Gastroenterol

D-Galactosamine liver injury: absorption of endotoxin and protective effect of small bowel and colon resection in rabbits

Proc Soc Exp Biol Med

Protective effect of colectomy in frog virus 3 hepatitis of rats. Possible role of endotoxin

J Infect Dis

Studies on the interaction between endotoxin and polymyxin B

J Infect Dis

Modification of human neutrophil response to endotoxin with polymyxin B sulfate

J Infect Dis

Endotoxin, sinusoidal cells, and liver injury