Cooperation between MASP-1 and MASP-2 in the generation of C3 convertase through the MBL pathway.
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.
Møller-Kristensen
Mette
M
Department of Medical Microbiology and Immunology, University of Aarhus, Denmark.
Thiel
Steffen
S
Sjöholm
Anders
A
Matsushita
Misao
M
Jensenius
Jens C
JC
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
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