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

• Published in: The Journal of clinical investigation Vol. 116; no. 5; pp. 1425 - 1434
• Main Authors: Selander, Barbro, Mårtensson, Ulla, Weintraub, Andrej, Holmström, Eva, Matsushita, Misao, Thiel, Steffen, Jensenius, Jens C, Truedsson, Lennart, Sjöholm, Anders G
• Format: Journal Article
• Language: English
• Published: United States American Society for Clinical Investigation 01.05.2006
• Subjects: Antibodies; Antigens; Basic Medicine; Biomedical research; Complement Activation; Complement C2 - physiology; Complement C3 - physiology; Enzyme-Linked Immunosorbent Assay; Escherichia coli - metabolism; Humans; Immunologi inom det medicinska området; Immunology; Immunology in the medical area; Lectins; Lipopolysaccharides - metabolism; Mannose-Binding Lectin - physiology; Mannose-Binding Protein-Associated Serine Proteases - metabolism; Medical and Health Sciences; Medical research; Medicin och hälsovetenskap; Medicine, Experimental; Medicinska och farmaceutiska grundvetenskaper; Microbiology in the medical area; Mikrobiologi inom det medicinska området; Oligosaccharides - chemistry; Protein research; Proteins; Recruitment; Salmonella; Salmonella enteritidis - metabolism; Salmonella typhimurium - metabolism; Sweden
• ISSN: 0021-9738; 1558-8238
• DOI: 10.1172/jci25982

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.