Immunological activity difference between native calreticulin monomers and oligomers.
Immunological activity difference between native calreticulin monomers and oligomers.
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天然钙网蛋白单体和寡聚物的免疫活性差异
DOI：
10.1371/journal.pone.0105502
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Gao XM
中科院分区：
文献类型：
--
作者：
He MC;Wang J;Wu J;Gong FY;Hong C;Xia Y;Zhang LJ;Bao WR;Gao XM
我们最近已经证明，重组小鼠钙网蛋白（rCRT）的免疫活性大大增加，主要归因于其自寡聚化。虽然天然CRT （nCRT）在体外应激条件下也会发生寡聚，但这种现象是否会发生在细胞内，以及nCRT单体和寡聚物之间的免疫活性差异尚不清楚。在这项研究中，我们展示了在“热&低pH”（42°C/pH 6.5）条件下转染细胞中CRT低聚物的形成。在类似条件下（42℃/pH 5.0），将小鼠单体nCRT （MnCRT）体外处理3小时，得到nCRT低聚物与单体混合物（OnCRT）。由此获得的OnCRT能被低聚rCRT免疫小鼠的2个单克隆抗体更好地识别。与MnCRT不同的是，OnCRT能够在小鼠体内引起crt特异性IgG的产生。OnCRT还刺激骨髓源性树突状细胞（bmdc）分泌显著高于MnCRT的TNF-α、IL-6和IL-12p40水平。我们假设可溶性CRT的寡聚可能发生在某些病理生理条件下（如超高热），由此产生的寡聚物可能表现出夸大的免疫刺激活性，从而与体内炎症反应有关。
We have recently demonstrated that the greatly increased immunological activities of recombinant murine calreticulin (rCRT) are largely attributed to its self-oligomerization. Although native CRT (nCRT) can also oligomerize under stress conditions in vitro, whether this phenomenon could occur inside cells and the immunological activity difference between nCRT monomers and oligomers remained unclear. In this study, we illustrated the formation of CRT oligomers in tranfectant cells under “heat & low pH” (42°C/pH 6.5) condition. The mixture of nCRT oligomers and monomers (OnCRT) was obtained after 3 hr treatment of murine monomeric nCRT (MnCRT) under similar condition (42°C/pH 5.0) in vitro. The OnCRT thus obtained was better recognized by 2 monoclonal Abs from mice that had been immunized with oligomeric rCRT. Unlike MnCRT, OnCRT was able to elicit CRT-specific IgG production in mice. OnCRT also stimulated bone-marrow derived dendritic cells (BMDCs) to secrete significantly higher levels of TNF-α, IL-6 and IL-12p40 than did MnCRT in vitro. We postulate that oligomerization of soluble CRT may occur under certain pathophysiological conditions (e.g. ultrahyperpyrexia) and the resultant oligomers may exhibit exaggerated immunostimulating activities, thereby affiliating the inflammatory responses in vivo.
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自身寡聚对于可溶性重组钙网蛋白增强免疫活性至关重要
影响因子：
3.7
作者：
Huang SH;Zhao LX;Hong C;Duo CC;Guo BN;Zhang LJ;Gong Z;Xiong SD;Gong FY;Gao XM
通讯作者：
Gao XM
影响因子：
4
作者：
Orr, AW;Elzie, CA;Murphy-Ullrich, JE
通讯作者：
Murphy-Ullrich, JE
影响因子：
11.5
作者：
Aguilera, Raquel;Saffie, Carlos;Salazar-Onfray, Flavio
通讯作者：
Salazar-Onfray, Flavio
影响因子：
4.8
作者：
Jeffery, Elise;Peters, Larry Robert;Raghavan, Malini
通讯作者：
Raghavan, Malini
影响因子：
6
作者：
Nanney, Lillian B.;Woodrell, Christopher D.;Gold, Leslie I.
通讯作者：
Gold, Leslie I.