title: Human monoclonal antibodies to glycolipid A that exhibit complement species-specific effector functions.
abstract: Two human IgM monoclonal anti-glycolipid A antibodies (MAbs) were evaluated for their abilities to bind to various endotoxins and pathogenic gram-negative bacteria and to activate complement pathways, thereby accomplishing bactericidal and opsonic effector functions. Both MAbs cross-reacted with glycolipid A mutant lipopolysaccharides from rough colony-forming gram-negative bacteria and with selected endotoxins from smooth colony-forming bacteria. However, MAb 10235 bound to all clinical isolates of Escherichia coli and Klebsiella pneumoniae tested but only very weakly to Pseudomonas aeruginosa, whereas MAb 10058 bound to all three genera. Several strains of serum-insensitive organisms were selected for evaluation of antigen-specific, complement-mediated effector functions for the two MAbs. Assessment of bactericidal and opsonic activities showed that neither MAb was able to activate complement from nonprimate species (mouse, rat, rabbit, guinea pig, or sheep). However, both MAbs were highly effective in using primate sources of serum complement to mediate these effector functions.
authors.affiliation: Department of Pharmacology, Cetus Corporation, Emeryville, California.
authors.forename: J L
authors.initials: JL
authors.lastname: Winkelhake
authors.forename: S S
authors.initials: SS
authors.lastname: Gauny
authors.forename: G
authors.initials: G
authors.lastname: Senyk
authors.forename: D
authors.initials: D
authors.lastname: Piazza
authors.forename: P
authors.initials: P
authors.lastname: Stevens
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000918:Antibody Specificity; D003167:Complement Activation; D003165:Complement System Proteins / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D006017:Glycolipids / Q000276:immunology*; D006090:Gram-Negative Bacteria / Q000276:immunology*; D006801:Humans; D008050:Lipid A / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology; D009895:Opsonin Proteins / Q000276:immunology; D013045:Species Specificity
chemical_list: D000911:Antibodies, Monoclonal; D006017:Glycolipids; D008050:Lipid A; D008070:Lipopolysaccharides; D009895:Opsonin Proteins; D003165:Complement System Proteins