Deconstructing the Lectin Pathway in the Pathogenesis of Experimental Inflammatory Arthritis: Essential Role of the Lectin Ficolin B and Mannose-Binding Protein-Associated Serine Protease 2.
Deconstructing the Lectin Pathway in the Pathogenesis of Experimental Inflammatory Arthritis: Essential Role of the Lectin Ficolin B and Mannose-Binding Protein-Associated Serine Protease 2.
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解构实验性炎症性关节炎发病机理中的凝集素途径：凝集素纤维蛋白B和甘露糖结合蛋白相关的丝氨酸蛋白酶2的重要作用。
DOI：
10.4049/jimmunol.1700119
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发表时间：
2017-09-01
期刊：
影响因子：
--
通讯作者：
Holers VM
中科院分区：
文献类型：
--
作者：
Banda NK;Acharya S;Scheinman RI;Mehta G;Takahashi M;Endo Y;Zhou W;Farrar CA;Sacks SH;Fujita T;Sekine H;Holers VM
补体在类风湿关节炎（RA）的发病机制中起重要作用。虽然已知旁路途径（AP）在RA模型中起关键的致病作用，但凝集素途径（LP）模式识别分子如纤维胶凝蛋白A（FCN A）、纤维胶凝蛋白B（FCN B）和凝集素-11（CL-11）以及活化酶MBL（甘露糖结合凝集素）相关的丝氨酸蛋白酶-2（MSP-2）的重要性尚不清楚。我们在这里表明，FCN A−/−和CL-11−/−小鼠对胶原抗体诱导的关节炎（CAIA）完全易感。相比之下，FCN B−/−和MASP-2−/−/sMAp−/−小鼠基本上受到保护，临床疾病活动性分别显著降低（p < 0.05）47%和70%。在FCN B−/−和MASP-2−/−/sMAp−/−小鼠中，滑膜巨噬细胞和中性粒细胞的组织学评分、C3、fD、FCN B沉积和浸润均类似地降低。我们的数据支持FCN B在CAIA的发展中起重要作用，可能通过关节中的配体识别和MASP活化，并且MASP-2也可能以C4非依赖性方式促进CAIA的发展。来自患有关节炎的FCN B−/−和MASP-2−/−/sMAp−/−小鼠的血清中的AP活性在粘附的抗胶原抗体上降低也支持致病性抗体以及另外的炎症相关配体被LP识别并在体内起作用以激活补体的假设。最后，我们还推测，在我们的研究中观察到的残留疾病是由AP和/或C2/C4旁路途径通过LP依赖性机制直接裂解C3驱动的。
Complement plays an important role in the pathogenesis of rheumatoid arthritis (RA). While the alternative pathway (AP) is known to play a key pathogenic role in models of RA, the importance of the lectin pathway (LP) pattern recognition molecules such as ficolin A (FCN A), ficolin B (FCN B) and collectin-11 (CL-11) as well as the activating enzyme MBL (mannose binding lectin)-associated serine protease-2 (MASP-2) are less well understood. We show here that FCN A−/− and CL-11−/− mice are fully susceptible to collagen antibody-induced arthritis (CAIA). In contrast, FCN B−/− and MASP-2−/−/sMAp−/− mice are substantially protected, with clinical disease activity decreased significantly (p < 0.05) by 47% and 70%, respectively. Histopathology scores, C3, fD, FCN B deposition and infiltration of synovial macrophages and neutrophils were similarly decreased in FCN B−/− and MASP-2−/−/sMAp−/− mice. Our data support that FCN B plays an important role in the development of CAIA, likely through ligand recognition in the joint and MASP activation, and that MASP-2 also contributes to the development of CAIA, likely in a C4-independent manner. Decreased AP activity in the sera from FCN B−/− and MASP-2−/−/sMAp−/− mice with arthritis on adherent anti-collagen antibodies also support the hypothesis that pathogenic antibodies as well as additional inflammation-related ligands are recognized by the LP and operate in vivo to activate complement. Finally, we also speculate that the residual disease seen in our studies is driven by the AP and/or the C2/C4 bypass pathway via the direct cleavage of C3 through a LP-dependent mechanism.
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DOI：
10.4049/jimmunol.1102310
发表时间：
2012-02-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Banda NK;Hyatt S;Antonioli AH;White JT;Glogowska M;Takahashi K;Merkel TJ;Stahl GL;Mueller-Ortiz S;Wetsel R;Arend WP;Holers VM
通讯作者：
Holers VM
DOI：
10.4049/jimmunol.0901826
发表时间：
2009-11-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Banda NK;Levitt B;Glogowska MJ;Thurman JM;Takahashi K;Stahl GL;Tomlinson S;Arend WP;Holers VM
通讯作者：
Holers VM
甘露糖结合凝集素相关的丝氨酸蛋白酶1/3的机理的补体途径激活。
影响因子：
3.6
作者：
Banda NK;Takahashi M;Takahashi K;Stahl GL;Hyatt S;Glogowska M;Wiles TA;Endo Y;Fujita T;Holers VM;Arend WP
通讯作者：
Arend WP
影响因子：
4.6
作者：
Banda, N. K.;Levitt, B.;Arend, W. P.
通讯作者：
Arend, W. P.
影响因子：
4.4
作者：
Banda, Nirmal K.;Takahashi, Kazue;Arend, William P.
通讯作者：
Arend, William P.