Small Mannose-binding Lectin-associated Protein Plays a Regulatory Role in the Lectin Complement Pathway.
From: Department of Immunology, Fukushima Medical University, 1-Hikariga-oka, Fukushima City 960-1295, Japan.
Journal of immunology (Baltimore, Md. : 1950)
- Publish Date: Dec 2006
- ISSN: 0022-1767
- Volume: 177
- Issue: 12
- Pages: 8626-32
- Medium: Print
- Language: English
- Citation (JAMA): Iwaki Daisuke, Kanno Kazuko, Takahashi Minoru, et al. Small Mannose-binding Lectin-associated Protein Plays a Regulatory Role in the Lectin Complement Pathway.. J. Immunol. Dec 2006;177:8626-32
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.
Mesh Headings (Keywords): Animals, Complement C4, Complement Pathway, Mannose-Binding Lectin, Hydrolysis, Immunity, Natural, Mannose-Binding Lectin, Mannose-Binding Protein-Associated Serine Proteases, Mice, Multiprotein Complexes
Check for Full Text / PubMed Unique Identifier (PMID): 17142762
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