Immunological activity difference between native calreticulin monomers and oligomers.
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...
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doaj-7c9eddf0b3634ebb95a3d366ecbf46da2020-11-24T21:50:27ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0198e10550210.1371/journal.pone.0105502Immunological activity difference between native calreticulin monomers and oligomers.Mi-chun HeJun WangJian WuFang-yuan GongChao HongYun XiaLi-juan ZhangWan-rong BaoXiao-Ming GaoWe 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.http://europepmc.org/articles/PMC4149419?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Mi-chun He Jun Wang Jian Wu Fang-yuan Gong Chao Hong Yun Xia Li-juan Zhang Wan-rong Bao Xiao-Ming Gao |
spellingShingle |
Mi-chun He Jun Wang Jian Wu Fang-yuan Gong Chao Hong Yun Xia Li-juan Zhang Wan-rong Bao Xiao-Ming Gao Immunological activity difference between native calreticulin monomers and oligomers. PLoS ONE |
author_facet |
Mi-chun He Jun Wang Jian Wu Fang-yuan Gong Chao Hong Yun Xia Li-juan Zhang Wan-rong Bao Xiao-Ming Gao |
author_sort |
Mi-chun He |
title |
Immunological activity difference between native calreticulin monomers and oligomers. |
title_short |
Immunological activity difference between native calreticulin monomers and oligomers. |
title_full |
Immunological activity difference between native calreticulin monomers and oligomers. |
title_fullStr |
Immunological activity difference between native calreticulin monomers and oligomers. |
title_full_unstemmed |
Immunological activity difference between native calreticulin monomers and oligomers. |
title_sort |
immunological activity difference between native calreticulin monomers and oligomers. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2014-01-01 |
description |
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. |
url |
http://europepmc.org/articles/PMC4149419?pdf=render |
work_keys_str_mv |
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