Serum amyloid P component binds to histones and activates the classical complement pathway.
Serum amyloid P component binds to histones and activates the classical complement pathway.
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DOI：
10.4049/jimmunol.149.11.3689
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发表时间：
1992-12
影响因子：
4.4
通讯作者：
P. Hicks;L. Saunero-Nava;T. D. Du Clos;C. Mold
中科院分区：
文献类型：
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作者：
P. Hicks;L. Saunero-Nava;T. D. Du Clos;C. Mold
五聚蛋白家族的两个成员 C 反应蛋白 (CRP) 和血清淀粉样蛋白 P 成分 (SAP) 与染色质结合，可能参与核物质的溶解和清除。先前的研究表明，CRP 与染色质的结合是由组蛋白介导的。 SAP 与 CRP 的不同之处在于能够与 DNA 结合，但 SAP 与组蛋白的结合尚未见报道。 CRP 是经典 C 途径的激活剂，在 CRP 和血清存在的情况下，染色质会发生 C 依赖性裂解。最近发现 SAP 低聚物与 C1q 结合并消耗总 C 和 C4，表明 SAP 也可以激活 C。本研究检测了 CRP 和 SAP 与组蛋白 H1 和 H2A 的结合以及结合后 C 的激活。观察到 SAP 与组蛋白 H1 和 H2A 的结合以及 SAP 与染色质的结合。与 CRP 不同，SAP 与染色质的结合不需要 H1。 SAP 部分抑制 CRP 与染色质和 H1 的结合。然而，两种五聚蛋白均不抑制另一种与 H2A 的结合。 CRP 或 SAP 与 H2A 结合会激活 SAP 耗尽血清中的 C，导致 C4 和 C3 沉积。 C 激活需要 C1q 并产生 C4d，表明它是通过经典途径发生的。这些发现表明，CRP 和 SAP 共享组蛋白和染色质结合，并且两种五聚蛋白都可以在配体结合后激活经典 C 途径。
Two members of the pentraxin family of proteins, C-reactive protein (CRP) and serum amyloid P component (SAP), bind to chromatin and may be involved in the solubilization and clearance of nuclear material. Previous studies demonstrated that CRP binding to chromatin is mediated by histones. SAP differs from CRP in being able to bind to DNA, but SAP binding to histones has not been reported. CRP is an activator of the classical C pathway, and C-dependent cleavage of chromatin in the presence of CRP and serum has been shown. Oligomers of SAP have recently been found to bind to C1q and consume total C and C4, indicating that SAP can activate C as well. The present study examined CRP and SAP binding to histones H1 and H2A and C activation after binding. SAP binding to histones H1 and H2A was observed as well as SAP binding to chromatin. In contrast to CRP, SAP binding to chromatin did not require H1. SAP partially inhibited CRP binding to chromatin and to H1. However, neither pentraxin inhibited binding of the other to H2A. Binding of either CRP or SAP to H2A activated C in SAP-depleted serum leading to the deposition of C4 and C3. C activation required C1q and produced C4d indicating that it occurred through the classical pathway. These findings demonstrate that CRP and SAP share histone as well as chromatin binding, and that both pentraxins can activate the classical C pathway after ligand binding.