Tanamoto K, Azumi S
Division of Microbiology, National Institute of Health Sciences, Tokyo, Japan.
J Immunol. 2000 Mar 15;164(6):3149-56. doi: 10.4049/jimmunol.164.6.3149.
The stimulation of both THP-1 and U937 human-derived cells by Salmonella lipid A preparations from various strains, as assessed by TNF-alpha induction and NF-kappaB activation, was found to be very low (almost inactive) compared with Escherichia coli lipid A, but all of the lipid As exerted strong activity on mouse cells and on Limulus gelation activity. Experiments using chemically synthesized E. coli-type hexaacylated lipid A (506) and Salmonella-type heptaacylated lipid A (516) yielded clearer results. Both lipid A preparations strongly induced TNF-alpha release and activated NF-kappaB in mouse peritoneal macrophages and mouse macrophage-like cell line J774-1 and induced Limulus gelation activity, although the activity of the latter was slightly weaker than that of the former. However, 516 was completely inactive on both THP-1 and U937 cells in terms of both induction of TNF-alpha and NF-kappaB activation, whereas 506 displayed strong activity on both cells, the same as natural E. coli LPS. In contrast to the action of the lipid A preparations, all the Salmonella LPSs also exhibited full activity on human cells. However, the polysaccharide portion of the LPS neither exhibited TNF-alpha induction activity on the cells when administered alone or together with lipid A nor inhibited the activity of the LPS. These results suggest that the mechanism of activation by LPS or the recognition of lipid A structure by human and mouse cells may differ. In addition, both 516 and lipid A from Salmonella were found to antagonize the 506 and E. coli LPS action that induced TNF-alpha release and NF-kappaB activation in THP-1 cells.
通过TNF-α诱导和NF-κB激活评估发现，与大肠杆菌脂多糖相比，来自各种菌株的沙门氏菌脂多糖制剂对THP-1和U937人源细胞的刺激作用非常低（几乎无活性），但所有脂多糖对小鼠细胞和鲎试剂凝胶化活性均表现出强活性。使用化学合成的大肠杆菌型六酰化脂多糖（506）和沙门氏菌型七酰化脂多糖（516）进行的实验得出了更清晰的结果。两种脂多糖制剂均能强烈诱导小鼠腹腔巨噬细胞和小鼠巨噬细胞样细胞系J774-1释放TNF-α并激活NF-κB，并诱导鲎试剂凝胶化活性，尽管后者的活性略弱于前者。然而，就TNF-α诱导和NF-κB激活而言，516对THP-1和U937细胞均完全无活性，而506对这两种细胞均表现出强活性，与天然大肠杆菌脂多糖相同。与脂多糖制剂的作用相反，所有沙门氏菌脂多糖在人源细胞上也均表现出完全活性。然而，脂多糖的多糖部分单独给药或与脂多糖一起给药时，对细胞均未表现出TNF-α诱导活性，也未抑制脂多糖的活性。这些结果表明，脂多糖的激活机制或人和小鼠细胞对脂多糖结构的识别可能存在差异。此外，发现来自沙门氏菌的516和脂多糖均能拮抗506和大肠杆菌脂多糖在THP-1细胞中诱导TNF-α释放和NF-κB激活的作用。
