Essential role for the lectin pathway in collagen antibody-induced arthritis revealed through use of adenovirus programming complement inhibitor MAp44 expression.
Essential role for the lectin pathway in collagen antibody-induced arthritis revealed through use of adenovirus programming complement inhibitor MAp44 expression.
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DOI：
10.4049/jimmunol.1400752
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发表时间：
2014-09-01
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;Mehta G;Kjaer TR;Takahashi M;Schaack J;Morrison TE;Thiel S;Arend WP;Holers VM
先前使用甘露糖结合凝集素（MBL）和补体C4缺陷小鼠的研究表明，在胶原抗体诱导的关节炎（CAIA）模型中，凝集素途径（LP）不是炎性关节炎发展所必需的。MBL、纤维胶凝蛋白和胶原凝集素-11是与三种丝氨酸蛋白酶MASP-1、MASP-2和MASP-3以及两种称为sMAP和MAp 44的MBL相关蛋白缔合的关键LP模式识别分子。最近的研究表明，MAp 44，MASP-1/3基因的选择性剪接产物，是识别分子与所有三种MASP结合的竞争性抑制剂。在这些研究中，我们检查了用编程表达人MAp 44的腺病毒（Ad）（AdhMAp 44）处理小鼠对CAIA发展的影响。在诱导CAIA之前，将AdhMAp 44和Ad编程绿色荧光蛋白（AdGFP）表达腹膜内注射到C57 BL/6野生型小鼠中。与注射AdGFP的小鼠相比，AdhMAp 44显著降低了81%的临床疾病活动评分（CDA）。类似地，AdhMAp 44预处理显著降低了炎症、血管翳、软骨和骨损伤以及软骨和滑膜中的C3沉积的组织病理学损伤评分。用AdmMAp 44（小鼠MAp 44的编程表达）处理的小鼠也显示出显著降低的CDA和组织病理学损伤评分。此外，AdhMAp 44的施用显著降低了Ross River病毒诱导的关节炎（一种LP依赖性模型）的严重程度。我们的研究提供了确凿的证据，完整的补体LP是启动CAIA所必需的，MAp 44可能是炎性关节炎的适当治疗。
Previous studies using mannose-binding lectin (MBL) and complement C4 deficient mice have suggested that the lectin pathway (LP) is not required for the development of inflammatory arthritis in the collagen antibody-induced arthritis (CAIA) model. MBL, ficolins and collectin-11 are key LP pattern recognition molecules that associate with three serine proteases, MASP-1, MASP-2 and MASP-3, and also with two MBL-associated proteins designated sMAP and MAp44. Recent studies have shown that MAp44, an alternatively spliced product of the MASP-1/3 gene, is a competitive inhibitor of the binding of the recognition molecules to all three MASPs. In these studies we examined the effect of treatment of mice with adenovirus (Ad) programmed to express human MAp44 (AdhMAp44) on the development of CAIA. AdhMAp44 and Ad programming Green fluorescent protein (AdGFP) expression were injected intraperitoneally in C57BL/6 wild-type mice prior to the induction of CAIA. AdhMAp44 significantly reduced the clinical disease activity score (CDA) by 81% compared to mice injected with AdGFP. Similarly, histopathologic injury scores for inflammation, pannus, cartilage and bone damage, as well as C3 deposition in the cartilage and synovium, were significantly reduced by AdhMAp44 pretreatment. Mice treated with AdmMAp44, programming expression of mouse MAp44, also showed significantly decreased CDA and histopathologic injury scores. Additionally, administration of AdhMAp44 significantly diminished the severity of Ross River Virus-induced arthritis, a LP-dependent model. Our study provides conclusive evidence that an intact complement LP is essential to initiate CAIA, and that MAp44 may be an appropriate treatment for inflammatory arthritis.
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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
影响因子：
4.4
作者：
Iwaki, Daisuke;Kanno, Kazuko;Fujita, Teizo
通讯作者：
Fujita, Teizo
影响因子：
2.2
作者：
Degn, Soren E.;Jensen, Lisbeth;Thiel, Steffen
通讯作者：
Thiel, Steffen
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.