Externalization and recognition by macrophages of large subunit of eukaryotic translation initiation factor 3 in apoptotic cells

Yuji Nakai, Akiko Shiratsuchi, Junko Manaka, Hiroshi Nakayama, Koji Takio, Jian Ting Zhang, Tatsuo Suganuma, Yoshinobu Nakanishi

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

We previously isolated a monoclonal antibody named PH2 that inhibits phosphatidylserine-mediated phagocytosis of apoptotic cells by macrophages [C. Fujii, A. Shiratsuchi, J. Manaka, S. Yonehara, Y. Nakanishi. Cell Death Differ. 8 (2001) 1113-1122]. We report here the identification of the cognate antigen. A protein bound by PH2 in Western blotting was identified as the 170-kDa subunit of eukaryotic translation initiation factor 3 (eIF3 p170/eIF3a). When eIF3a was expressed in a culture cell line as a protein fused to green fluorescence protein, the fusion protein was detected at the cell surface only after the induction of apoptosis. The same phenomenon was seen when the localization of endogenous eIF3a was determined using anti-eIF3a antibody, and eIF3a seemed to be partially degraded during apoptosis. Furthermore, bacterially expressed N-terminal half of eIF3a fused to glutathione S-transferase bound to the surface of macrophages and inhibited phagocytosis of apoptotic cells by macrophages when it was added to phagocytosis reactions. These results collectively suggest that eIF3a translocates to the cell surface upon apoptosis, probably after partial degradation, and bridges apoptotic cells and macrophages to enhance phagocytosis.

Original languageEnglish (US)
Pages (from-to)137-148
Number of pages12
JournalExperimental Cell Research
Volume309
Issue number1
DOIs
StatePublished - Sep 10 2005

Keywords

  • Apoptosis
  • eIF3 p170
  • eIF3a
  • Macrophage
  • Monoclonal antibody
  • Phagocytosis
  • Translation initiation factor

ASJC Scopus subject areas

  • Cell Biology

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    Nakai, Y., Shiratsuchi, A., Manaka, J., Nakayama, H., Takio, K., Zhang, J. T., Suganuma, T., & Nakanishi, Y. (2005). Externalization and recognition by macrophages of large subunit of eukaryotic translation initiation factor 3 in apoptotic cells. Experimental Cell Research, 309(1), 137-148. https://doi.org/10.1016/j.yexcr.2005.05.006