Human natural anti-Gal IgG regulates alternative complement pathway activation on bacterial surfaces.
One percent of circulating IgG in humans recognizes galactose alpha 1,3 galactose residues (anti-Gal) and is synthesized in response to stimulation by enteric bacteria. In this study, we found that the prevalence of binding of anti-Gal to blood isolates is significantly higher than its binding to normal stool isolates. When anti-Gal bound onto the lipopolysaccharide of a representative blood isolate, Serratia marcescens #21, it blocked its alternative complement pathway (ACP) lysis and made the organism serum resistant. In contrast, when anti-Gal bound to the capsular polysaccharide of a serum sensitive Serratia, #7, it increased ACP killing of this strain. The mechanism of blockade of ACP lysis by anti-Gal did not involve a decrease in the number of C3 molecules deposited onto Serratia #21 or an inhibition of the binding of C3b to its LPS, nor did it change the iC3b and C3d degradation products of bound C3b or prevent membrane attack complex formation on this organism. Our findings suggest that the effect of anti-Gal on immune lysis is dependent on the bacterial outer membrane structure to which it binds. We postulate that anti-Gal may play a role in the survival of selected Enterobacteriacae in Gram-negative sepsis by blocking ACP-mediated lysis of such bacteria by the nonimmune host, and that this effect depends on where anti-Gal finds its epitope on the bacterial outer membrane.
Hamadeh
R M
RM
Center for Immunochemistry, Veterans Administration Medical Center, San Francisco, California 94121.
Jarvis
G A
GA
Galili
U
U
Mandrell
R E
RE
Zhou
P
P
Griffiss
J M
JM
D003176:Complement C3 / Q000378:metabolism; D003186:Complement C9 / Q000378:metabolism; D015938:Complement Membrane Attack Complex / Q000378:metabolism; D003170:Complement Pathway, Alternative; D005690:Galactose / Q000276:immunology*; D006090:Gram-Negative Bacteria / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000502:physiology*; D008070:Lipopolysaccharides / Q000378:metabolism; D012705:Serratia / Q000276:immunology
D003176:Complement C3; D003186:Complement C9; D015938:Complement Membrane Attack Complex; D007074:Immunoglobulin G; D008070:Lipopolysaccharides; D005690:Galactose