title: M-ficolin, an innate immune defence molecule, binds patterns of acetyl groups and activates complement.
abstract: Ficolins play a role in the innate immune defence as pathogen-associated molecular pattern recognition molecules. Three ficolins are found in humans: H-ficolin, L-ficolin and M-ficolin. L-ficolin and H-ficolin circulate in blood in complexes with mannan-binding lectin-associated serine proteases (MASPs) and are capable of activating the complement system. L-ficolin shows affinity for acetylated compounds and binds to various capsulated strains of bacteria. H-ficolin has been shown to bind Aerococcus viridans. Less is known about M-ficolin, but it is thought to be present only on monocytes. We have synthesized recombinant M-ficolin and find that it, in a manner similar to L-ficolin, is able to bind to acetylated compounds and to associate with recombinant MASP-2. Upon binding to M-ficolin ligands, the associated MASP-2 zymogen is activated and cleaves C4, thus triggering the complement system. We developed a monoclonal rat anti-human-M/L-ficolin antibody and verified by flow cytometric analysis the presence of ficolin on the surface of peripheral blood monocytes.
authors.affiliation: Department of Medical Microbiology and Immunology, University of Aarhus, Aarhus, DK, Denmark. pdf@microbiology.au.dk
authors.forename: P D
authors.initials: PD
authors.lastname: Frederiksen
authors.forename: S
authors.initials: S
authors.lastname: Thiel
authors.forename: C B
authors.initials: CB
authors.lastname: Larsen
authors.forename: J C
authors.initials: JC
authors.lastname: Jensenius
mesh_terms: D000107:Acetylation; D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000276:immunology; D001667:Binding, Competitive; D015153:Blotting, Western; D002118:Calcium / Q000737:chemistry; D002460:Cell Line; D003167:Complement Activation / Q000276:immunology*; D003181:Complement C4 / Q000378:metabolism; D015935:Complement C4b / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D037102:Lectins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D050606:Mannose-Binding Protein-Associated Serine Proteases / Q000378:metabolism; D008565:Membrane Proteins / Q000032:analysis; D008970:Molecular Weight; D009000:Monocytes / Q000737:chemistry; D011485:Protein Binding / Q000276:immunology; D051381:Rats; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000302:isolation & purification; D012709:Serum Albumin / Q000737:chemistry / Q000276:immunology; D000097604:Ficolins
chemical_list: D000911:Antibodies, Monoclonal; D002118:Calcium; D003181:Complement C4; D015935:Complement C4b; D037102:Lectins; D050606:Mannose-Binding Protein-Associated Serine Proteases; D008565:Membrane Proteins; D011994:Recombinant Proteins; D012709:Serum Albumin; D000097604:Ficolins; C105296:MASP2 protein, human