title: Immunological activity difference between native calreticulin monomers and oligomers.
abstract: 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.
authors.affiliation: Institutes of Biology and Medical Sciences, Soochow University, Suzhou, Jiangsu Province, China.
authors.forename: Mi-chun
authors.initials: MC
authors.lastname: He
authors.affiliation: Institutes of Biology and Medical Sciences, Soochow University, Suzhou, Jiangsu Province, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Internal Medicine Center of Rheumatoid Diseases, the First Hospital of Soochow University, Suzhou, Jiangsu Province, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wu
authors.affiliation: Institutes of Biology and Medical Sciences, Soochow University, Suzhou, Jiangsu Province, China.
authors.forename: Fang-yuan
authors.initials: FY
authors.lastname: Gong
authors.affiliation: Institutes of Biology and Medical Sciences, Soochow University, Suzhou, Jiangsu Province, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Hong
authors.affiliation: Institutes of Biology and Medical Sciences, Soochow University, Suzhou, Jiangsu Province, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Xia
authors.affiliation: Institutes of Biology and Medical Sciences, Soochow University, Suzhou, Jiangsu Province, China.
authors.forename: Li-juan
authors.initials: LJ
authors.lastname: Zhang
authors.affiliation: Institutes of Biology and Medical Sciences, Soochow University, Suzhou, Jiangsu Province, China.
authors.forename: Wan-rong
authors.initials: WR
authors.lastname: Bao
authors.affiliation: Institutes of Biology and Medical Sciences, Soochow University, Suzhou, Jiangsu Province, China.
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Gao
mesh_terms: D000818:Animals; D000906:Antibodies / Q000097:blood / Q000276:immunology*; D001854:Bone Marrow Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D037282:Calreticulin / Q000737:chemistry* / Q000276:immunology* / Q000494:pharmacology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology; D006358:Hot Temperature; D006863:Hydrogen-Ion Concentration; D007114:Immunization / Q000379:methods; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D053762:Interleukin-12 Subunit p40 / Q000276:immunology / Q000378:metabolism; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D055503:Protein Multimerization / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
chemical_list: D000906:Antibodies; D037282:Calreticulin; D000939:Epitopes; D007074:Immunoglobulin G; D053762:Interleukin-12 Subunit p40; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha