Distinct roles in phagocytosis of the early and late increases of cell surface calreticulin induced by oxaliplatin

Autor: Kenju Matsusaka, Yutaro Azuma, Yuki Kaga, Saeka Uchida, Yuri Takebayashi, Takashi Tsuyama, Shusuke Tada
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Biochemistry and Biophysics Reports, Vol 29, Iss , Pp 101222- (2022)
Druh dokumentu: article
ISSN: 2405-5808
DOI: 10.1016/j.bbrep.2022.101222
Popis: Calreticulin (CRT), a chaperone typically located in the endoplasmic reticulum (ER), is known to translocate to the cell surface in response to anticancer drugs. Cell surface CRT (ecto-CRT) on apoptotic or pre-apoptotic cells serves as an “eat me” signal that can promote phagocytosis. In this study, we observed the biphasic (early transient and late sustained) increase of ecto-CRT on HT-29 cells after treatment with oxaliplatin (L-OHP). To investigate the role of ecto-CRT that accumulates in the early and late phases as “eat me” signals, we examined the phagocytosis of HT-29 cells by macrophage-like cells and dendritic cell (DC) -like cells prepared from THP-1 cells. The results indicated that the early ecto-CRT-expressed cells were phagocytosed by immature DC-like cells, and the late ecto-CRT-expressed cells were phagocytosed primarily by macrophage-like cells, while mature DC-like cells did not respond to the either class of ecto-CRT-expressed cells. Both types of phagocytotic events were inhibited by CRT Blocking Peptide, suggesting that such events depended on the ecto-CRT. Our results suggested that the early increase of ecto-CRT is related to phagocytosis as part of immunogenic cell death (ICD), while the late increase of ecto-CRT is related to the removal of apoptotic cells by macrophages.
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