Dissociation of endotoxic activities in a chemically synthesized lipid A precursor after acetylation

Abstract

In a previous study, a chemically synthesized disaccharide precursor of lipid A (406; identical to lipid IV A) was shown to have dramatically reduced lethality, B-cell mitogenicity, and tumor necrosis factor induction in macrophages when its hydroxyl groups were replaced with either succinyl or acetyl residues (K. Tanamoto, FEBS Lett. 351:325-329, 1994). Succinylated 406 was found to lose Limulus amoebocyte lysate gelation activity completely as a result of the modification (about 10 5-fold), too, as expected. However, acetyl 406, surprisingly, exhibited activity comparable to that of the original 406. Both succinylated and acetylated 406 lost pyrogenicity completely. These results indicate that one of the typical endotoxic activities was dissociated from the others and that the ability to induce Limulus amoebocyte lysate gelation is not always representative of endotoxin activity.

Cyanobacterial lipopolysaccharides and human health – a review

“…This is a highly sensitive test, though there are trade-offs in terms of specificity, with other bacterial products such as peptidoglycan and glucan capable of registering positive responses [ 49 , 202 , 203 ]. The assay may not always be a reliable predictor of cellular and in vivo responses [ 204 ]. Seydel et al [ 205 ] suggest that, while the LAL assay is useful for detecting and quantifying LPS in blood products, it is not a measure of endotoxicity.…”