Human mannose-binding protein activates the alternative complement pathway and enhances serum bactericidal activity on a mannose-rich isolate of Salmonella.
The human mannose-binding protein (MBP) is a multimeric serum protein that is divided into three domains, a cysteine-rich NH2-terminal domain that stabilizes the collagen alpha helix of the second domain and a third COOH-terminal carbohydrate recognition domain. Previous studies have shown that both native and recombinant human MBP bind to wild-type virulent Salmonella montevideo that expresses a mannose-rich lipopolysaccharide. Interaction with MBP results in opsonization and killing by phagocytes. In this report we show that low concentration of MBP (less than 10 micrograms/ml) markedly enhance complement deposition via the alternative complement pathway on S. montevideo. Despite structural similarities between MBP and the C1q subcomponent of the first complement component, MBP did not restore classical pathway activity to C1q-deficient serum, nor did it activate C1s when added to a mixture of C1r and C1s. In the presence of MBP the C3 bound to S. montevideo during incubation in serum was in the form of C3b and iC3b at a ratio of 1:2. Presensitization of S. montevideo with MBP rendered this normally serum resistant organism susceptible to complement-mediated killing. These results emphasize that MBP and complement cooperate in first line defense of the nonimmune host.
Schweinle
J E
JE
Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892.
Ezekowitz
R A
RA
Tenner
A J
AJ
Kuhlman
M
M
Joiner
K A
KA
D000595:Amino Acid Sequence; D001770:Blood Bactericidal Activity / Q000187:drug effects*; D002352:Carrier Proteins / Q000494:pharmacology*; D003167:Complement Activation / Q000187:drug effects*; D003172:Complement C1 / Q000276:immunology; D003176:Complement C3 / Q000378:metabolism; D003170:Complement Pathway, Alternative / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007700:Kinetics; D008070:Lipopolysaccharides / Q000032:analysis; D008351:Mannans / Q000494:pharmacology; D008358:Mannose / Q000032:analysis; D037241:Mannose-Binding Lectins; D008969:Molecular Sequence Data; D012475:Salmonella / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
D002352:Carrier Proteins; D003172:Complement C1; D003176:Complement C3; D008070:Lipopolysaccharides; D008351:Mannans; D037241:Mannose-Binding Lectins; D008358:Mannose