L-ficolin specifically binds to lipoteichoic acid, a cell wall constituent of Gram-positive bacteria, and activates the lectin pathway of complement

J Immunol. 2004 Jan 15;172(2):1198-202. doi: 10.4049/jimmunol.172.2.1198.

Abstract

The lectin pathway of complement is activated when a carbohydrate recognition complex and associated serine proteases binds to the surface of a pathogen. Three recognition subcomponents have been shown to form active initiation complexes: mannan-binding lectin (MBL), L-ficolin, and H-ficolin. The importance of MBL in antimicrobial host defense is well recognized, but the role of the ficolins remains largely undefined. This report shows that L-ficolin specifically binds to lipoteichoic acid (LTA), a cell wall component found in all Gram-positive bacteria. Immobilized LTA from Staphylococcus aureus binds L-ficolin complexes from sera, and these complexes initiate lectin pathway-dependent C4 turnover. C4 activation correlates with serum L-ficolin concentration, but not with serum MBL levels. L-ficolin binding and corresponding levels of C4 turnover were observed on LTA purified from other clinically important bacteria, including Streptococcus pyogenes and Streptococcus agalactiae. None of the LTA preparations bound MBL, H-ficolin, or the classical pathway recognition molecule, C1q.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / metabolism
  • Carrier Proteins / blood
  • Carrier Proteins / metabolism*
  • Cell Wall / immunology
  • Cell Wall / metabolism
  • Complement Activation / immunology*
  • Complement C4 / metabolism
  • Ficolins
  • Gram-Positive Bacteria / immunology*
  • Gram-Positive Bacteria / metabolism*
  • Humans
  • Hydrolysis
  • Immunity, Innate
  • Lectins / metabolism*
  • Lipopolysaccharides / metabolism*
  • Mannose-Binding Lectin / metabolism
  • Mannose-Binding Protein-Associated Serine Proteases
  • Serine Endopeptidases / metabolism
  • Staphylococcus aureus / immunology
  • Staphylococcus aureus / metabolism
  • Streptococcaceae / immunology
  • Streptococcaceae / metabolism
  • Teichoic Acids / metabolism*

Substances

  • Adjuvants, Immunologic
  • Carrier Proteins
  • Complement C4
  • Lectins
  • Lipopolysaccharides
  • Mannose-Binding Lectin
  • Teichoic Acids
  • lipoteichoic acid
  • Mannose-Binding Protein-Associated Serine Proteases
  • Serine Endopeptidases