title: Cooperation between MASP-1 and MASP-2 in the generation of C3 convertase through the MBL pathway.
abstract: The complement system is an important part of the innate immune system. Three pathways, the classical, the alternative and the lectin pathway, lead to the cleavage of complement factor C3, a central event in the activation of the complement system. We investigated the deposition of C3b (solid-phase C3 activation product) on a mannan-coated surface at high concentration of human serum (17%). At these conditions, mannan-binding lectin (MBL) promoted the activation of C3 through the combined action of MBL-associated serine protease (MASP)-1 and MASP-2 without appreciable involvement of the alternative pathway. In serum depleted of MASP-1, MASP-2 and MASP-3, we observed synergetic effect of reconstitution with MASP-1 and MASP-2. This was inhibited by MASP-3. No C3b deposition was observed with C2- or C4-depleted serum. Depletion of factor B had no effect on the MBL-MASP-promoted C3b deposition. Our results demonstrate a function of the orphan protease MASP-1 by providing evidence that this enzyme collaborates with MASP-2 in the generation of C3 convertase, a process observable at high serum concentration, but not at low serum concentration.
authors.affiliation: Department of Medical Microbiology and Immunology, University of Aarhus, Denmark.
authors.forename: Mette
authors.initials: M
authors.lastname: Møller-Kristensen
authors.forename: Steffen
authors.initials: S
authors.lastname: Thiel
authors.forename: Anders
authors.initials: A
authors.lastname: Sjöholm
authors.forename: Misao
authors.initials: M
authors.lastname: Matsushita
authors.forename: Jens C
authors.initials: JC
authors.lastname: Jensenius
mesh_terms: D000818:Animals; D003167:Complement Activation / Q000502:physiology*; D050577:Complement C3-C5 Convertases / Q000096:biosynthesis*; D003179:Complement C3b / Q000378:metabolism; D006801:Humans; D037601:Mannose-Binding Lectin / Q000378:metabolism*; D037241:Mannose-Binding Lectins / Q000378:metabolism; D050606:Mannose-Binding Protein-Associated Serine Proteases / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout
chemical_list: D037601:Mannose-Binding Lectin; D037241:Mannose-Binding Lectins; D003179:Complement C3b; D050577:Complement C3-C5 Convertases; C084067:MASP1 protein, human; C105296:MASP2 protein, human; D050606:Mannose-Binding Protein-Associated Serine Proteases