The level of mannan-binding protein regulates the binding of complement-derived opsonins to mannan and zymosan at low serum concentrations.
When sera diluted to 5% in a buffer containing calcium and magnesium were incubated with mannan-coated ELISA plates, C4 fragments, properdin and factor B were bound to the plates as well as the expected opsonic C3 fragments, C3b and C3bi. The calcium-dependent lectin mannan-binding protein, which is structurally similar to C1q, was also shown to bind in this assay and analysis of sera from 179 healthy blood donors revealed that the binding levels of all these proteins were highly significantly correlated. Results obtained with a previously described C3b opsonic assay using zymosan also correlated with the mannan-binding levels. When the sera were diluted to 5% in the presence of Mg-EGTA there was no detectable binding of complement proteins to the mannan surface, confirming that no alternative pathway activation occurred at this serum concentration. When sera were diluted to 5% in a buffer containing EDTA in order to study immunoglobulin binding in the absence of complement activation, the levels of bound IgG1, IgG2, IgG3, IgA and IgM antibodies were found to be completely unrelated to the C3bi binding levels previously observed. The results suggest that in this experimental system using low concentrations of serum, mannan-binding protein initiates an antibody-independent mechanism of cleavage of the classical pathway component C4, which subsequently regulates the degree of cleavage of C3 and recruitment of alternative pathway proteins.
Super
M
M
Department of Immunology, Institute of Child Health, London, England.
Levinsky
R J
RJ
Turner
M W
MW
D002352:Carrier Proteins / Q000097:blood / Q000502:physiology*; D037222:Collectins; D003179:Complement C3b / Q000378:metabolism; D015932:Complement C3c / Q000378:metabolism; D003181:Complement C4 / Q000378:metabolism; D006801:Humans; D008351:Mannans / Q000276:immunology / Q000378:metabolism*; D009895:Opsonin Proteins / Q000378:metabolism*; D015054:Zymosan / Q000276:immunology / Q000378:metabolism*
D002352:Carrier Proteins; D037222:Collectins; D003181:Complement C4; D008351:Mannans; D009895:Opsonin Proteins; D003179:Complement C3b; D015932:Complement C3c; D015054:Zymosan