2011 Fiscal Year Final Research Report
The lectin complement pathway is involved in activation of the alternative pathway
| Project/Area Number |
21390086
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General medical chemistry
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| Research Institution | Fukushima Medical University |
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Principal Investigator |
FUJITA Teizo 福島県立医科大学, 医学部, 名誉教授 (20134223)
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| Co-Investigator(Kenkyū-buntansha) |
IWAKI Daisuke 福島県立医科大学, 医学部, 助教 (10315492)
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| Project Period (FY) |
2009 – 2011
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| Keywords | 免疫学 / 自然免疫 / 補体 / レクチン経路 / 第2経路 / MASP / 感染症 |
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| Research Abstract |
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 thought to be a key enzyme that cleaves C4 and C2 to assemble a C3 convertase(C4b2a). However, a 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 mouse model, and found that the deficient mice lacked alternative pathway activation, because 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-3 was able to activate Bf of the alternative pathway. Thus, MASP-1 and MASP-3 seems to be involved in activation of both the lectin and alternative pathways, thereby, playing a central role in innate immunity.
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Research Products
(15 results)
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[Journal Article] L-Ficolin Binds to the Glycoproteins Hemagglutinin and Neuraminidase and Inhibits Influenza A Virus Infection Both in vitro and in vivo2012
Author(s)
Pan Q, Chen H, Wang F, Jeza VT, Hou W, Zhao Y, Xiang T, Zhu Y, Endo Y, Fujita T, Zhang XL.
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Journal Title
J Innate Immun
Volume: 4
Pages: 312-324
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[Journal Article] Targeting of mannan-binding lectin-associated serine protease-2 confers protection from myocardial and gastrointestinal ischemia/reperfusion injury2011
Author(s)
Schwaeble W J, Lynch N J, Clark J E, Marber M, Samani N J, All Y M, Dudler T, Parent B, Lhotta K, Wallis R, Farrar C A, Sacks S, Lee H, Zhang M, Iwaki D, Takahashi M, Fujita T, Tedford C E, and Stover C M.
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Journal Title
Proc Natl Acad Sci U S A
Volume: 108
Pages: 7523-7528
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[Journal Article] Mechanisms of mannose-binding lectin-associated serine proteases-1/3 activation of the alternative pathway of complement2011
Author(s)
Banda N K, Takahashi M, Takahashi K, Stahl G L, Hyatt S, Glogowska M, Wiles T A, Endo Y, Fujita T, Michael Holers V, and Arend W P
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Journal Title
Mol Immunol
Volume: 49
Pages: 281-289
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