title: Collectin-11/MASP complex formation triggers activation of the lectin complement pathway--the fifth lectin pathway initiation complex.
abstract: Collectins and ficolins are important in the clearance of endogenous and exogenous danger materials. A new human collectin-11 was recently identified in low concentration in serum in complex with mannose-binding lectin (MBL)/ficolin-associated serine proteases. Collectin-11 binds to carbohydrate residues present on various microorganisms. Thus, we hypothesized that collectin-11 could be a novel initiation molecule in the lectin pathway of complement. We can show that collectin-11 associates with all the known MBL-associated serine proteases (MASP-1, MASP-2 and MASP-3) as well as the lectin complement pathway regulator MAP-1. Furthermore, we found that complex formation between recombinant collectin-11 and recombinant MASP-2 on Candida albicans leads to deposition of C4b. Native collectin-11 in serum mediated complement activation and deposition of C4b and C3b, and formation of the terminal complement complex on C. albicans. Moreover, spiking collectin-11-depleted serum, which did not mediate complement activation, with recombinant collectin-11 restored the complement activation capability. These results define collectin-11 as the fifth recognition molecule in the lectin complement pathway in addition to MBL, ficolin-1, ficolin-2 and ficolin-3.
authors.affiliation: Department of Clinical Immunology, Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Ying Jie
authors.initials: YJ
authors.lastname: Ma
authors.forename: Mikkel-Ole
authors.initials: MO
authors.lastname: Skjoedt
authors.forename: Peter
authors.initials: P
authors.lastname: Garred
mesh_terms: D002176:Candida albicans / Q000276:immunology* / Q000378:metabolism; D003179:Complement C3b / Q000276:immunology / Q000378:metabolism; D015935:Complement C4b / Q000276:immunology / Q000378:metabolism; D037582:Complement Pathway, Mannose-Binding Lectin / Q000276:immunology*; D006801:Humans; D037102:Lectins / Q000276:immunology / Q000378:metabolism; D037601:Mannose-Binding Lectin / Q000276:immunology* / Q000378:metabolism; D050606:Mannose-Binding Protein-Associated Serine Proteases / Q000276:immunology* / Q000378:metabolism; D046912:Multiprotein Complexes / Q000276:immunology* / Q000378:metabolism; D000097604:Ficolins
chemical_list: D003179:Complement C3b; D015935:Complement C4b; D037102:Lectins; D037601:Mannose-Binding Lectin; D050606:Mannose-Binding Protein-Associated Serine Proteases; D046912:Multiprotein Complexes; D000097604:Ficolins