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细胞外 DNA 的起源和特性:从 PAMP 到 DAMP。

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

机构信息

Medical Research Service, Durham Veterans Administration Medical Center, Durham, NC 27705, USA.

出版信息

Clin Immunol. 2012 Jul;144(1):32-40. doi: 10.1016/j.clim.2012.04.006. Epub 2012 May 3.

DOI:10.1016/j.clim.2012.04.006
PMID:22659033
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3724456/
Abstract

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.

摘要

DNA 是一种聚合大分子,其生物活性取决于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,主要发生在细胞死亡时,包括细胞凋亡或坏死,以及 NETosis。虽然细菌 DNA 因其 CpG 基序而成为一种有效的免疫刺激物,但哺乳动物 DNA 通常是无活性的,通过与核、细胞质和血清蛋白结合而获得活性,从而促进其进入细胞内刺激内部 DNA 传感器,包括 Toll 样受体 9。在这些蛋白质中,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。这些发现表明,DNA 的免疫特性是可改变和多样化的,反映了其所处的环境和与之结合的分子种类。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1636/3724456/4acab600a2f4/nihms-382227-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1636/3724456/4acab600a2f4/nihms-382227-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1636/3724456/4acab600a2f4/nihms-382227-f0001.jpg

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