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Membrane-bound heat shock proteins facilitate the uptake of dying cells and cross-presentation of cellular antigen

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Abstract

Heat shock proteins (HSPs) were originally identified as stress-responsive proteins and serve as molecular chaperones in different intracellular compartments. Translocation of HSPs to the cell surface and release of HSPs into the extracellular space have been observed during the apoptotic process and in response to a variety of cellular stress. Here, we report that UV irradiation and cisplatin treatment rapidly induce the expression of membrane-bound Hsp60, Hsp70, and Hsp90 upstream the phosphatidylserine exposure. Membrane-bound Hsp60, Hsp70 and Hsp90 could promote the release of IL-6 and IL-1β as well as DC maturation by the evaluation of CD80 and CD86 expression. On the other hand, Hsp60, Hsp70 and Hsp90 on cells could facilitate the uptake of dying cells by bone marrow-derived dendritic cells. Lectin-like oxidized LDL receptor-1 (LOX-1), as a common receptor for Hsp60, Hsp70, and Hsp90, is response for their recognition and mediates the uptake of dying cells. Furthermore, membrane-bound Hsp60, Hsp70 and Hsp90 could promote the cross-presentation of OVA antigen from E.G7 cells and inhibition of the uptake of dying cells by LOX-1 decreases the cross-presentation of cellular antigen. Therefore, the rapid exposure of HSPs on dying cells at the early stage allows for the recognition by and confers an activation signal to the immune system.

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Abbreviations

HSP:

Heat shock protein

Hsp60:

Heat shock protein 60

Hsp70:

Heat shock protein 70

Hsp90:

Heat shock protein 90

LOX-1:

Lectin-like oxidized LDL receptor-1

triHsps:

Hsp60, Hsp70 and Hsp90

PtdSer:

Phosphatidylserine

BMDC:

Bone-derived dendritic cell

UV:

Ultraviolet

TLR:

Toll-like receptor

DAMP:

Damage-associated molecular pattern

MHC:

Major histocompatibility complex

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Acknowledgments

We appreciate Dr. T. Sawamura for kindly providing LOX-1 plasmid and Dr. Y. Wan for kindly providing the T cell hybridoma B3Z. This work was supported by National Basic Research Program of China (973 Program 2012CB822104, 2010CB912104), State Key Project Specialized for Infectious Diseases (2012ZX10001006-003, 2012ZX10002-008), Shanghai Leading Academic Discipline Project (B110), the National Natural Science Fund (30900266, 31010103906, and 31170766), the Natural Science Foundation of the Jiangsu Higher Education Institutions of China (15KJA310003) and Research Fund for the Doctoral Program of Higher Education of China (20090071120053).

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    Authors and Affiliations

    1. Key Laboratory of Glycoconjugate Research, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China

      Haiyan Zhu, Weicheng Wu, Miaomiao Shao, Lan Wang & Jianxin Gu

    2. Jiangsu Patent Examination Assistance Center Under Sipo, Suzhou, Jiangsu, 215163, China

      Xiaoyun Fang

    3. Department of Pathogen Biology, Medical College, Nantong University, Nantong, 226001, China

      Dongmei Zhang

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    1. Haiyan Zhu
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    Haiyan Zhu and Xiaoyun Fang have contributed equally to this work.

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    Zhu, H., Fang, X., Zhang, D. et al. Membrane-bound heat shock proteins facilitate the uptake of dying cells and cross-presentation of cellular antigen. Apoptosis 21, 96–109 (2016). https://doi.org/10.1007/s10495-015-1187-0

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