Nontoxic forms of lipopolysaccharides, poorly cleared in vivo, are present in variable amounts in phenol-extracted...

A radiolabeled lipopolysaccharide (LPS) from Salmonella choleraesuis was as toxic for galactosamine-treated mice as the unlabeled preparation. After intravenous injection, a large proportion (37%) of the labeled material remained in the circulation. This circulating form of LPS was not toxic, even when reextracted with phenol, and remained in the circulation when reinjected into mice. Furthermore, toxic and nontoxic constituents were directly isolated in vitro by hydrophobic gel chromatography of the radiolabeled LPS preparation. The nontoxic form, of lower molecular weight according to its electrophoretic migration, did not react with an anti-lipid A monoclonal antibody but reacted with polymyxin B and was as active on pre-B and B cells as the unfractionated LPS preparation. The results of this study suggest that some LPS constituents of phenol-extracted endotoxin preparations are not toxic for galactosamine-sensitized mice and are not trapped by appropriate LPS-binding sites in the liver as efficiently as are the toxic forms.