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D-半乳糖胺肝毒性与内毒素敏感性相关,并由小鼠的淋巴网状细胞介导。

D-Galactosamine hepatotoxicity is associated with endotoxin sensitivity and mediated by lymphoreticular cells in mice.

作者信息

Chojkier M, Fierer J

出版信息

Gastroenterology. 1985 Jan;88(1 Pt 1):115-21. doi: 10.1016/s0016-5085(85)80142-6.

DOI:10.1016/s0016-5085(85)80142-6
PMID:3880554
Abstract

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.

摘要

携带相同突变脂多糖基因(Lpsd)的两种品系小鼠(C57BL/10ScN和C3H/HeJ)对内毒素(LPS)的毒性作用具有抗性,它们对D-半乳糖胺的肝毒性作用也有部分抗性。通过血清丙氨酸氨基转移酶测定,LPS抗性品系中由D-半乳糖胺诱导的肝损伤程度仅为密切相关的LPS敏感小鼠品系的10%-30%。同样,内毒素抗性品系中的组织病理学变化不如LPS易感小鼠明显。通过将LPS敏感品系的脾细胞转移到经致死剂量照射的LPS抗性小鼠中,我们确定对D-半乳糖胺的易感性是由淋巴网状细胞介导的。抗辐射的脾细胞转移了D-半乳糖胺敏感性,提示巨噬细胞发挥了作用。我们并未排除淋巴细胞也能传递对D-半乳糖胺反应的可能性。这些结果表明,在小鼠中,D-半乳糖胺敏感性与内毒素敏感性相关,且前者由淋巴网状细胞而非肝细胞介导。

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