Short leucine-rich glycoproteins of the extracellular matrix display diverse patterns of complement interaction and activation.
Short leucine-rich glycoproteins of the extracellular matrix display diverse patterns of complement interaction and activation.
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DOI：
10.1016/j.molimm.2008.09.018
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发表时间：
2009-02
影响因子：
3.6
通讯作者：
Blom, Anna M.
中科院分区：
文献类型：
--
作者：
Sjoberg, Andreas P.;Manderson, Gavin A.;Morgelin, Matthias;Day, Anthony J.;Heinegard, Dick;Blom, Anna M.
细胞外基质由结构大分子和其他具有调节功能的蛋白质组成。在大多数组织中发现的后一类分子的一个重要家族是小亮氨酸重复蛋白（slrp）。我们之前已经证明，SLRP纤维调节蛋白直接与C1q结合并激活补体的经典途径。在本研究中，我们进一步研究了slrp和补体之间的相互作用。骨粘附素与纤维调节素一样，结合C1q并强烈激活经典途径，而在终端途径中则有中度激活。这可以通过纤维调节素和骨粘附素与因子H（补体的主要可溶性抑制剂）的相互作用来解释。此外，软骨粘附素被发现结合C1q并激活补体，尽管程度较小。软骨粘附素也结合因子H.我们证实了已发表的数据，表明biglycan和decorin结合C1q但不激活补体。在这项研究中，尽管lumican对C1q的亲和力低于对biglycan和decorin的亲和力，但也发现了类似的模式。此外，使用电子显微镜和放射性标记的SLRP，我们证明了C1q上两种不同类型的SLRP结合位点，分别是头部和茎，其中只有头部的结合似乎是激活的。我们提出slrp在涉及细胞外基质的疾病中，特别是那些以慢性炎症为特征的疾病，如类风湿关节炎、动脉粥样硬化、骨关节炎和慢性阻塞性肺疾病，在补体激活的调节中发挥作用。
The extracellular matrix consists of structural macromolecules and other proteins with regulatory functions. An important family of the latter class of molecules found in most tissues is the small leucine-rich repeat proteins (SLRPs). We have previously shown that the SLRP fibromodulin binds directly to C1q and activates the classical pathway of complement. In the present study we further examine the interactions between SLRPs and complement. Osteoadherin, like fibromodulin, binds C1q and activates the classical pathway strongly while moderate activation is seen in the terminal pathway. This can be explained by the interaction of fibromodulin and osteoadherin with factor H, a major soluble inhibitor of complement. Also, chondroadherin was found to bind C1q and activate complement, albeit to a lesser extent. Chondroadherin also binds factor H. We confirm published data showing that biglycan and decorin bind C1q but do not activate complement. In this study a similar pattern is seen for lumican although its affinity for C1q is lower than for biglycan and decorin. Furthermore, using electron microscopy and radiolabeled SLRPs, we demonstrate two different classes of SLRP binding sites on C1q, to head and stalk respectively, where only binding to the head appears to be activating. We propose a role for SLRPs in the regulation of complement activation in diseases involving the extracellular matrix, particularly those characterized by chronic inflammation such as rheumatoid arthritis, atherosclerosis, osteoarthritis and chronic obstructive lung disease.
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DOI：
10.1073/pnas.0501536102
发表时间：
2005-05-17
影响因子：
11.1
作者：
Hageman, GS;Anderson, DH;Allikmets, R
通讯作者：
Allikmets, R
影响因子：
4.8
作者：
Månsson, B;Wenglén, C;Heinegård, D
通讯作者：
Heinegård, D
影响因子：
7.6
作者：
Lucchini, M;Couble, ML;Farges, JC
通讯作者：
Farges, JC
影响因子：
4.8
作者：
Önnerfjord, P;Heathfield, TF;Heinegård, D
通讯作者：
Heinegård, D
影响因子：
3.2
作者：
DAY, AJ;WILLIS, AC;SIM, RB
通讯作者：
SIM, RB