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Surface expression of a C-terminal alpha-helix region in heat shock protein 72 on murine LL/2 lung carcinoma can be recognized by innate immune sentinels. | LitMetric

Surface expression of a C-terminal alpha-helix region in heat shock protein 72 on murine LL/2 lung carcinoma can be recognized by innate immune sentinels.

Mol Immunol

Laboratory of Global Food Science, Department of Natural Resources, Graduate School of Global Environmental Studies, Kyoto University, Kitashirakawa-Oiwake-cho, Sakyo-ku, Kyoto 606-8502, Japan.

Published: April 2009

AI Article Synopsis

Article Abstract

Surface expression of Hsp70 members has been previously reported on human tumor cell lines. Here we examined how the inducible mouse Hsp72 can be expressed on the surface of two types of murine tumor cell lines in response to non-lethal heat shock. Exposure to 42 degrees C for 2h led to the intracellular production of Hsp72 for both murine LL/2 lung carcinoma and B16 melanoma cells. Flow cytometric analyses showed that living LL/2 carcinoma, but not B16 melanoma, transported a fraction of inducible Hsp72 to the cell-surface membrane. Induction of the surface expression of Hsp72 occurred upon non-lethal heat shock only when Hsp72 expression was forced to be elevated in B16 transfectants. Hsp72 expressed on the LL/2 cell surface was detected by the monoclonal antibody that recognized the epitope of 504-617 amino acid residues, but not by another antibody with the epitope of 122-264 residues. When we analyzed the binding of recombinant full-length Hsp72 to mouse splenocytes, significant binding was observed for innate immune cells such as CD11b(+)-, CD11c(+)-, or NK1.1(+)-cells. The recombinant variants obtained by truncation of the C-terminal helical region of Hsp72 exhibited more robust binding to these innate immune cells in a similar fashion, however, further deletion offered less binding to those immunocytes. Two fragment variants lacking the N-terminal nucleotide-binding domain were found to extensively bind to peritoneal macrophages. Taken together with these results, it thus follows that the sentinels in an innate immune system, macrophages, dendritic cells and NK cells, can be involved in the surveillance of functionally aberrant cells through the recognition of a specific C-terminal structure of Hsp70 as a danger signal in living cells.

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Source
http://dx.doi.org/10.1016/j.molimm.2008.11.020DOI Listing

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