Human anti-endotoxin antibody HA-1A mediates complement-dependent binding of Escherichia coli J5 lipopolysaccharide to complement receptor type 1 of human erythrocytes and neutrophils.
HA-1A has been shown clinically to decrease mortality in septic patients with gram-negative bacteremia. In this study, the ability of HA-1A to augment the serum complement-dependent immune adherence of 125I-labeled Escherichia coli J5 lipopolysaccharide (LPS) to human erythrocytes (RBC) and polymorphonuclear leukocytes (PMNL) was evaluated. In vitro studies indicated three things: HA-1A mediates immune adherence of 125I-J5 LPS to human RBC and PMNL in a dose-dependent manner; under these conditions, high concentrations of LPS (400 ng/mL) could be specifically bound. Immune adherence occurs via the classical complement pathway as demonstrated by its calcium dependence; HA-1A-J5 LPS-C' immune complexes bound to CR1 on human RBC and PMNL. PMNL binding and internalization of immune complexes was demonstrated by trypsin stripping of externally bound immune complexes. These studies support the proposal that HA-1A can lower the bioavailability of endotoxin by mediating binding and potential clearance of LPS via human RBC through the reticuloendothelial system or via direct internalization by peripheral blood PMNL.
Krieger
J I
JI
Immunobiology Research and Development, Centocor, Inc., Malvern, Pennsylvania.
Fletcher
R C
RC
Siegel
S A
SA
Fearon
D T
DT
Neblock
D S
DS
Boutin
R H
RH
Taylor
R P
RP
Daddona
P E
PE
D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D000936:Antigen-Antibody Complex / Q000378:metabolism*; D003179:Complement C3b / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D015935:Complement C4b / Q000187:drug effects / Q000378:metabolism; D003171:Complement Pathway, Classical; D004306:Dose-Response Relationship, Immunologic; D004731:Endotoxins / Q000378:metabolism*; D004912:Erythrocytes / Q000378:metabolism*; D004926:Escherichia coli; D006801:Humans; D007075:Immunoglobulin M / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000378:metabolism*; D009504:Neutrophils / Q000378:metabolism*; D011951:Receptors, Complement / Q000378:metabolism; D013997:Time Factors
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000936:Antigen-Antibody Complex; D004731:Endotoxins; D007075:Immunoglobulin M; D008070:Lipopolysaccharides; D011951:Receptors, Complement; C044101:endotoxin, Escherichia coli; D003179:Complement C3b; D015935:Complement C4b; C068069:nebacumab