Activation of the lectin complement pathway by H-ficolin (Hakata antigen)

J Immunol. 2002 Apr 1;168(7):3502-6. doi: 10.4049/jimmunol.168.7.3502.

Abstract

Ficolins are a group of proteins which consist of a collagen-like domain and a fibrinogen-like domain. In human serum, there are two types of ficolins named L-ficolin/P35 and H-ficolin (Hakata Ag), both of which have lectin activity. We recently demonstrated that L-ficolin/P35 is associated with mannose-binding lectin (MBL)-associated serine proteases (MASP) 1 and 2 and small MBL-associated protein (sMAP), and that the complex activates the lectin pathway. In this study, we report the characterization of H-ficolin in terms of its ability to activate complement. Western blotting analysis showed the presence of MASP-1, MASP-2, MASP-3, and sMAP in H-ficolin preparations isolated from Cohn Fraction III. The MASPs in the preparations had proteolytic activities against C4, C2, and C3 in the fluid phase. When H-ficolin preparations were bound to anti-H-ficolin Ab which had been coated on ELISA plates, they activated C4, although no C4 activation was noted when anti-MBL and anti-L-ficolin/P35 were used. H-ficolin binds to PSA, a polysaccharide produced by Aerococcus viridans. C4 was activated by H-ficolin preparations bound to PSA which had been coated on ELISA plates. These results indicate that H-ficolin is a second ficolin which is associated with MASPs and sMAP, and which activates the lectin pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / metabolism
  • Bacterial Adhesion / immunology
  • Binding Sites, Antibody
  • Carrier Proteins / metabolism
  • Collectins
  • Complement Activating Enzymes / isolation & purification
  • Complement Activating Enzymes / metabolism
  • Complement Activating Enzymes / physiology
  • Complement Activation / immunology*
  • Glycoproteins / immunology
  • Glycoproteins / metabolism
  • Glycoproteins / physiology*
  • Humans
  • Lectins / metabolism*
  • Mannose-Binding Protein-Associated Serine Proteases
  • Polysaccharides, Bacterial / metabolism
  • Protein Binding / immunology
  • Serine Endopeptidases / immunology
  • Serine Endopeptidases / isolation & purification
  • Serine Endopeptidases / metabolism
  • Serine Endopeptidases / physiology
  • Streptococcaceae / metabolism

Substances

  • Antibodies, Monoclonal
  • Carrier Proteins
  • Collectins
  • FCN3 protein, human
  • Glycoproteins
  • Lectins
  • Polysaccharides, Bacterial
  • Complement Activating Enzymes
  • MASP2 protein, human
  • Mannose-Binding Protein-Associated Serine Proteases
  • Serine Endopeptidases