Anti-endotoxin monoclonal antibodies protect by enhancing bacterial and endotoxin clearance
R. S. Burd, C. S. Cody, C. S. Raymond and D. L. Dunn
Department of Surgery, University of Minnesota, Minneapolis.
In this study, we sought to determine the mechanism(s) by which a
type-specific anti-lipopolysaccharide monoclonal antibody (an IgG directed
against the O-antigen polysaccharide region of Salmonella minnesota
lipopolysaccharide) and its F(ab')2 fragments protect during gram-negative
bacterial peritonitis and endotoxemia in mice. During peritoneal infection,
(1) IgG significantly decreased mortality, bacteremia, and endotoxemia at
all time points compared with saline solution pretreatment and (2) F(ab')2
fragments reduced mortality at 24 hours but not thereafter, and had no
effect on bacteremia but reduced endotoxemia compared with saline solution
pretreatment. In the endotoxin model, IgG pretreatment significantly
reduced mortality compared with saline solution pretreatment, while F(ab')2
fragments had no significant effect on mortality. No difference in
endotoxemia was observed in mice that received IgG, F(ab')2 fragments, or
saline solution pretreatment during endotoxemia. These results suggest that
type-specific anti-lipopolysaccharide monoclonal antibodies protect by
Fc-mediated clearance of both bacteria and endotoxin.