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Mannan-binding lectin activates C3 and the alternative complement pathway without involvement of C2
Barbro Selander, … , Lennart Truedsson, Anders G. Sjöholm
Barbro Selander, … , Lennart Truedsson, Anders G. Sjöholm
Published May 1, 2006
Citation Information: J Clin Invest. 2006;116(5):1425-1434. https://doi.org/10.1172/JCI25982.
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Research Article Immunology

Mannan-binding lectin activates C3 and the alternative complement pathway without involvement of C2

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Abstract

Lectin pathway activation of C3 is known to involve target recognition by mannan-binding lectin (MBL) or ficolins and generation of classical pathway C3 convertase via cleavage of C4 and C2 by MBL-associated serine protease 2 (MASP-2). We investigated C3 activation in C2-deficient human sera and in sera with other defined defects of complement to assess other mechanisms through which MBL might recruit complement. The capacity of serum to support C3 deposition was examined by ELISA using microtiter plates coated with O antigen–specific oligosaccharides derived from Salmonella typhimurium, S. thompson, and S. enteritidis corresponding to serogroups B, C, and D (BO, CO, and DO). MBL bound to CO, but not to BO and DO, and efficiently supported C3 deposition in the absence of C2, C4, or MASP-2. The existence of an MBL-dependent C2 bypass mechanism for alternative pathway–mediated C3 activation was clearly demonstrated using CO, solid-phase mannan, and E. coli LPS. MASP-1 might contribute, but was not required for C3 deposition in the model used. Independent of MBL, specific antibodies to CO supported C3 deposition through classical and alternative pathways. MBL-dependent C2 bypass activation could be particularly important in various inherited and acquired complement deficiency states.

Authors

Barbro Selander, Ulla Mårtensson, Andrej Weintraub, Eva Holmström, Misao Matsushita, Steffen Thiel, Jens C. Jensenius, Lennart Truedsson, Anders G. Sjöholm

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Figure 5

Dose-dependent enhancement of C3 deposition by purified MBL (A ), purified MBL/MASP complexes (B ), and specific anti-CO IgG antibodies (C ) in C2D:21 serum (combined C2 and MBL deficiency).

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                  Dose-dependent enhancement of C3 deposition by purifi...
The serum was used at a final concentration of 25%. Shown are experiments in which CO-coated wells (1,000 ng/well) were presensitized with MBL in VBS before addition of serum (A) and in which MBL/MASP complexes were added directly to the serum (B) applied to the CO-coated wells. In experiments with specific antibodies (C), wells coated with BO or CO antigen were presensitized in VBS-EDTA with polyclonal IgG (Endobulin) containing defined amounts of the specific antibodies. After washing, incubation of the bound specific antibodies with the C2-deficient serum was carried out at 37°C for 30 minutes. Each experiment was performed in duplicate and was repeated once with similar results.

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