The origin and properties of extracellular DNA: from PAMP to DAMP.

The origin and properties of extracellular DNA: from PAMP to DAMP.
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DOI:
10.1016/j.clim.2012.04.006
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发表时间:
2012-07
期刊:
Clinical immunology (Orlando, Fla.)
影响因子:
--
通讯作者:
Pisetsky DS
Pisetsky DS
中科院分区:
其他
文献类型:
--
作者:
Pisetsky DS

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DNA是一种聚合物大分子,其生物活性依赖于其位置以及与相关分子的结合。在细胞内,DNA是遗传信息的来源,并与组蛋白结合形成核小体。然而,DNA可以离开细胞,进入细胞外空间,主要是在细胞死亡期间,无论是细胞死亡,还是死亡或坏死,以及网织红细胞增多。细菌DNA通过其CpG基序是一种有效的免疫刺激剂,而哺乳动物DNA通常是不活跃的,它可以通过与核蛋白、胞浆蛋白和血清蛋白结合来获得活性,这些蛋白促进其被细胞摄取,从而刺激内部DNA传感器,包括Toll样受体9。在这些蛋白中,抗DNA自身抗体可以与DNA形成免疫复合物,刺激浆细胞样树突状细胞产生1型干扰素。综上所述,这些发现表明,DNA的免疫特性是可变的和多样化的,反映了它的背景和连接的分子阵列。
DNA is a polymeric macromolecule whose biological activities depend on location as well as binding to associated molecules. Inside the cell, DNA is the source of genetic information and binds histones to form nucleosomes. DNA can exit the cell, however, to enter the extracellular space primarily during cell death, either apoptosis or necrosis, as well as NETosis. While bacterial DNA is a potent immune stimulant by virtue of its CpG motifs, mammalian DNA, which is ordinarily inactive, can acquire activity by associating with nuclear, cytoplasmic and serum proteins which promote its uptake into cells to stimulate internal DNA sensors, including toll-like receptor 9. Among these proteins, anti-DNA autoantibodies can form immune complexes with DNA to stimulate plasmacytoid dendritic cells to produce type 1 interferon. Together, these findings suggest that the immune properties of DNA are mutable and diverse, reflecting its context and the array of attached molecules.
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