D-Galactosamine hepatotoxicity is associated with endotoxin sensitivity and mediated by lymphoreticular cells in mice.
Two strains of mice (C57BL/10ScN and C3H/HeJ) that carry the same mutant lipopolysaccharide gene (Lpsd) 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 aminotransferase, the degree of liver injury induced by D-galactosamine in 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.
D000818:Animals; D004351:Drug Resistance; D004731:Endotoxins / Q000633:toxicity*; D005688:Galactosamine / Q000378:metabolism / Q000633:toxicity*; D005796:Genes; D007116:Immunization, Passive; D007728:Kupffer Cells / Q000187:drug effects*; D008070:Lipopolysaccharides / Q000235:genetics; D008099:Liver / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000187:drug effects / Q000276:immunology / Q000528:radiation effects; D014916:Whole-Body Irradiation
D004731:Endotoxins; D008070:Lipopolysaccharides; D005688:Galactosamine