L-ficolin specifically binds to lipoteichoic acid, a cell wall constituent of Gram-positive bacteria, and activates the lectin pathway of complement.
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.
Lynch
Nicholas J
NJ
Department of Infection, Immunity and Inflammation, University of Leicester, University Road, Leicester LE1 9HN, U.K.
Roscher
Silke
S
Hartung
Thomas
T
Morath
Siegfried
S
Matsushita
Misao
M
Maennel
Daniela N
DN
Kuraya
Mikio
M
Fujita
Teizo
T
Schwaeble
Wilhelm J
WJ
D000276:Adjuvants, Immunologic / Q000378:metabolism; D002352:Carrier Proteins / Q000097:blood / Q000378:metabolism*; D002473:Cell Wall / Q000276:immunology / Q000378:metabolism; D003167:Complement Activation / Q000276:immunology*; D003181:Complement C4 / Q000378:metabolism; D006094:Gram-Positive Bacteria / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D006868:Hydrolysis; D007113:Immunity, Innate; D037102:Lectins / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000378:metabolism*; D037601:Mannose-Binding Lectin / Q000378:metabolism; D050606:Mannose-Binding Protein-Associated Serine Proteases; D012697:Serine Endopeptidases / Q000378:metabolism; D013211:Staphylococcus aureus / Q000276:immunology / Q000378:metabolism; D013289:Streptococcaceae / Q000276:immunology / Q000378:metabolism; D013682:Teichoic Acids / Q000378:metabolism*; D000097604:Ficolins
D000276:Adjuvants, Immunologic; D002352:Carrier Proteins; D003181:Complement C4; D037102:Lectins; D008070:Lipopolysaccharides; D037601:Mannose-Binding Lectin; D050606:Mannose-Binding Protein-Associated Serine Proteases; D012697:Serine Endopeptidases; D013682:Teichoic Acids; D000097604:Ficolins; C009900:lipoteichoic acid