Consideration on endotoxin that is not detectable by the Limulus Amebocyte Lysate test

Abstract

Recent study on the activation of the Limulus amebocyte lysate （LAL） revealed that the dimerization is necessary for the activation of Factor C on lipopolysaccharide （LPS） aggregates. Factor B is also an LPS-binding protein and is activated on the same LPS aggregates. This indicates that the activation of the LAL needs a space on endotoxin aggregates. Therefore, monomeric LPS cannot activate the LAL. It may be difficult to be monomeric for LPS in water-based solutions. In animal blood, however, monomeric LPS can exist because soluble CD14 （sCD14） can bind to monomeric LPS. The sCD14/LPS complex is probably not detectable by the LAL because it is monomeric. This indicates that there may be undetectable LPS in animal blood. Detection of the undetectable LPS in animal blood can be important to understand the effect of LPS on animals. Methods to detect the undetectable LPS should be developed in the future.