Membrane-bound heat shock proteins facilitate the uptake of dying cells and cross-presentation of cellular antigen.
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.
Key Laboratory of Glycoconjugate Research, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China.
Haiyan
H
Zhu
Jiangsu Patent Examination Assistance Center Under Sipo, Suzhou, Jiangsu, 215163, China.
Xiaoyun
X
Fang
Department of Pathogen Biology, Medical College, Nantong University, Nantong, 226001, China.
Dongmei
D
Zhang
Key Laboratory of Glycoconjugate Research, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China.
Weicheng
W
Wu
Key Laboratory of Glycoconjugate Research, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China.
Miaomiao
M
Shao
Key Laboratory of Glycoconjugate Research, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China. wanglan1102@yahoo.com.
Lan
L
Wang
Key Laboratory of Glycoconjugate Research, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China.
Jianxin
J
Gu
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D018122:B7-1 Antigen / Q000235:genetics / Q000276:immunology; D051940:B7-2 Antigen / Q000235:genetics / Q000276:immunology; D016466:CHO Cells; D002462:Cell Membrane / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D018834:Chaperonin 60 / Q000235:genetics* / Q000276:immunology; D003412:Cricetulus; D045142:Cross-Priming; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D005786:Gene Expression Regulation; D018922:HL-60 Cells; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics* / Q000276:immunology; D018841:HSP90 Heat-Shock Proteins / Q000235:genetics* / Q000276:immunology; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics / Q000276:immunology; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D024101:Mitochondrial Proteins / Q000235:genetics* / Q000276:immunology; D010047:Ovalbumin / Q000494:pharmacology; D010718:Phosphatidylserines / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding; D051127:Scavenger Receptors, Class E / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction
D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D018834:Chaperonin 60; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; C557066:Hspd1 protein, mouse; D053583:Interleukin-1beta; D015850:Interleukin-6; D024101:Mitochondrial Proteins; C495138:Olr1 protein, mouse; D010718:Phosphatidylserines; D051127:Scavenger Receptors, Class E; C577686:interleukin-6, mouse; D010047:Ovalbumin
Apoptosis; Cross-presentation; Cytokine expression; DC maturation; HSPs; LOX-1