Mechanisms of Neutralization of Endotoxin by Monoclonal IgG Antibodies to Lipopolysaccharide

Abstract

Endotoxemia is a serious and cumbersome illness, especially for immunocompromised patients who are susceptible to drug-resistant enteric bacteria. In an attempt to explore immunoprophylactic measures applicable to humans, protective efficacies of antibodies to lipopolysaccharide (LPS) have been extensively studied. Thus antibodies to heterologous R core (Braude et al. 1977; Davis et al. 1978; Marks et al. 1982; Ziegler et al.1982) as well as those to homologous O polysaccharides (Freedman 1959; Dunn et al. 1985) are now believed to be able, at least to some extent, to prevent animals and humans from developing endotoxemia. However, it is not yet clear how antibodies to O and R resions located at different spacings from lipid A can equally neutralize the toxic activities of LPS, whereas antibodies to the toxic lipid A moiety itself often fail to do so. In this study, we have prepared mouse monoclonal antibodies (mAbs) of the IgG class to these three regions of LPS and compared their effects on the toxic activities of LPS in vivo and in vitro to look into the mechanism for neutralization by these antibodies.