title: Small mannose-binding lectin-associated protein plays a regulatory role in the lectin complement pathway.
abstract: Mannose-binding lectin (MBL) and ficolins are pattern recognition proteins acting in innate immunity, and they trigger the activation of the lectin complement pathway through MBL-associated serine proteases (MASPs). Upon activation of the lectin pathway, MASP-2 cleaves C4 and C2. A truncated form of MASP-2, named small MBL-associated protein (sMAP), is also associated with MBL/ficolin-MASP complexes. To clarify the role of sMAP, we have generated sMAP-deficient (sMAP(-/-)) mice by targeted disruption of the sMAP-specific exon. Because of the gene disruption, the expression level of MASP-2 was also decreased in sMAP(-/-) mice. When recombinant sMAP (rsMAP) and recombinant MASP-2 (rMASP-2) reconstituted the MBL-MASP-sMAP complex in deficient serum, the binding of these recombinant proteins to MBL was competitive, and the C4 cleavage activity of the MBL-MASP-sMAP complex was restored by the addition of rMASP-2, whereas the addition of rsMAP attenuated the activity. Therefore, MASP-2 is essential for the activation of C4 and sMAP plays a regulatory role in the activation of the lectin pathway.
authors.affiliation: Department of Immunology, Fukushima Medical University, 1-Hikariga-oka, Fukushima City 960-1295, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Iwaki
authors.forename: Kazuko
authors.initials: K
authors.lastname: Kanno
authors.forename: Minoru
authors.initials: M
authors.lastname: Takahashi
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Endo
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Lynch
authors.forename: Wilhelm J
authors.initials: WJ
authors.lastname: Schwaeble
authors.forename: Misao
authors.initials: M
authors.lastname: Matsushita
authors.forename: Masaru
authors.initials: M
authors.lastname: Okabe
authors.forename: Teizo
authors.initials: T
authors.lastname: Fujita
mesh_terms: D000818:Animals; D003181:Complement C4 / Q000378:metabolism; D037582:Complement Pathway, Mannose-Binding Lectin / Q000276:immunology*; D006868:Hydrolysis; D007113:Immunity, Innate; D037601:Mannose-Binding Lectin / Q000378:metabolism; D050606:Mannose-Binding Protein-Associated Serine Proteases / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D046912:Multiprotein Complexes / Q000276:immunology / Q000378:metabolism
chemical_list: D003181:Complement C4; D037601:Mannose-Binding Lectin; D046912:Multiprotein Complexes; C491340:MASP-2 protein, mouse; D050606:Mannose-Binding Protein-Associated Serine Proteases