title: The role of MASP-1/3 in complement activation.
abstract: The complement system, which consists of more than 30 plasma and cell surface proteins, is activated by three pathways: the classical, lectin, and alternative pathways, leading to the generation of opsonins and pathogen destruction. In the lectin pathway, mannose-binding lectin (MBL) and ficolins act as pattern recognition molecules for pathogens, resulting in the activation of MBL-associated serine proteases (MASPs: MASP-1, MASP-2, and MASP-3). Among these proteases, MASP-2 is a key enzyme that cleaves C4 and C2 to assemble a C3 convertase (C4b2a). However, the physiological function of MASP-1 and MASP-3 remains unclear. To investigate the roles of MASP-1 and MASP-3, we generated a MASP-1- and MASP-3-deficient (M1/3 KO) mouse model and found that the deficient mice lacked alternative pathway activation because factor D (Df) remained as a proenzyme in the serum. MASP-1 and MASP-3 were able to convert the proenzyme of Df to an active form in vitro. In addition, MASP-1 was able to activate MASP-2 and MASP-3 as C1r activates C1s. Thus, MASP-1 and MASP-3 seem to be involved in activation of both the lectin and alternative pathways.
authors: Department of Immunology, Fukushima Medical University School of Medicine, 1-Hikariga-oka, Fukushima 960-1295, Japan.
authors: Hideharu
authors: H
authors: Sekine
authors: Minoru
authors: M
authors: Takahashi
authors: Daisuke
authors: D
authors: Iwaki
authors: Teizo
authors: T
authors: Fujita
mesh_terms: D000818:Animals; D003167:Complement Activation / Q000502:physiology*; D003170:Complement Pathway, Alternative / Q000187:drug effects; D006801:Humans; D007107:Immune System / Q000502:physiology; D037102:Lectins / Q000502:physiology; D050606:Mannose-Binding Protein-Associated Serine Proteases / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics
chemical_list: D037102:Lectins; C084067:MASP1 protein, human; C105296:MASP2 protein, human; D050606:Mannose-Binding Protein-Associated Serine Proteases