The anti-lipid A antibody HA-1A binds to rough gram-negative bacteria, fixes complement and facilitates binding to erythrocyte CR1 (CD35).
MoAbs to bacterial cell wall lipopolysaccharide are currently under evaluation for the treatment of Gram-negative sepsis. The mode of action of these reagents remains poorly understood. In this study we examined the ability of radiolabelled HA-1A (an IgM anti-lipid A MoAb) to bind in vitro to Salmonella minnesota (Re 595), Escherichia coli, and Streptococcus pyogenes. HA-1A was able to bind specifically to the 'rough' mutant Salm. minnesota, but not to a 'smooth' E. coli, or Strep. pyogenes. Binding to Salm. minnesota led to complement fixation which resulted in bacterial adherence to erythrocyte CR1, suggesting a possible mechanism whereby the antibody might enhance clearance of bacteria by facilitating delivery to the fixed mononuclear phagocytic system. We were not able to demonstrate the formation of immune complexes between free lipopolysaccharide and HA-1A in the presence of serum, nor the enhancement of complement-mediated binding of HA-1A:Salm. minnesota immune complexes to erythrocytes by antibiotic treatment. Binding of HA-1A to small bacterial fragments was, however, demonstrable after in vitro treatment with a beta-lactam antibiotic, which disrupts the bacterial cell wall, but not with gentamicin, an aminoglycoside antibiotic which blocks protein synthesis.
Tonoli
M
M
Department of Medicine, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK.
Davies
K A
KA
Norsworthy
P J
PJ
Cohen
J
J
Walport
M J
MJ
D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000907:Antibodies, Bacterial / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000936:Antigen-Antibody Complex / Q000378:metabolism; D001667:Binding, Competitive; D003167:Complement Activation; D004912:Erythrocytes / Q000276:immunology*; D006090:Gram-Negative Bacteria / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D066298:In Vitro Techniques; D008050:Lipid A / Q000276:immunology*; D017463:Receptors, Complement 3b / Q000378:metabolism*; D012475:Salmonella / Q000187:drug effects / Q000276:immunology
D000900:Anti-Bacterial Agents; D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D008050:Lipid A; D017463:Receptors, Complement 3b