Cited by 346Phagocytosis and Immune RegulationErythrocyte Function and PathophysiologyCellular transport and secretion

Phosphatidylserine-dependent engulfment by macrophages of nuclei from erythroid precursor cells

Yoshida, Hideyuki, Kawane, Kohki, Koike, Masato, Mori, Yoshimi, Uchiyama, Yasuo, Nagata, Shigekazu·2005·Nature

Abstract

Definitive erythropoiesis usually occurs in the bone marrow or fetal liver, where erythroblasts are associated with a central macrophage in anatomical units called 'blood islands'. Late in erythropoiesis, nuclei are expelled from the erythroid precursor cells and engulfed by the macrophages in the blood island. Here we show that the nuclei are engulfed by macrophages only after they are disconnected from reticulocytes, and that phosphatidylserine, which is often used as an 'eat me' signal for apoptotic cells, is also used for the engulfment of nuclei expelled from erythroblasts. We investigated the mechanism behind the enucleation and engulfment processes by isolating late-stage erythroblasts from the spleens of phlebotomized mice. When these erythroblasts were cultured, the nuclei protruded spontaneously from the erythroblasts. A weak physical force could disconnect the nuclei from the reticulocytes. The released nuclei contained an undetectable level of ATP, and quickly exposed phosphatidylserine on their surface. Fetal liver macrophages efficiently engulfed the nuclei; masking the phosphatidylserine on the nuclei with the dominant-negative form of milk-fat-globule EGF8 (MFG-E8) prevented this engulfment.

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Crossref · 10.1038/nature03964

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Authors
Yoshida, H., Kawane, K., Koike, M., Mori, Y., Uchiyama, Y., & Nagata, S.
Affiliations
  • The University of Osaka (JP)
  • Japan Science and Technology Agency (JP)
Corresponding author
Nagata, Shigekazu
Venue
Nature
Published
2005-09
Volume
437
Issue
7059
Pages
754-758
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
OpenAlex
W1999184263
Cited by
346
References
32
Citations by year
2026: 7 · 2025: 13 · 2024: 19 · 2023: 12 · 2022: 12 · 2021: 26 · 2020: 15 · 2019: 9 · 2018: 17 · 2017: 25 · 2016: 14 · 2015: 15 · 2014: 16 · 2013: 16 · 2012: 22
FWCI
6.50
Type
journal article
Language
en
Open access
closed
Locations
  • Nature (publishedVersion)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
  • Health Sciences › Medicine › Physiology › Erythrocyte Function and Pathophysiology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
Keywords
phosphatidylserine, macrophage engulfment, erythropoiesis, erythroblasts, blood islands, MFG-E8, phagocytosis, reticulocytes
MeSH terms
Adenosine Triphosphate, Animals, Antigens, Surface, Calcium, Cell Nucleus, Endocytosis, Erythroblasts, Erythropoiesis, Flow Cytometry, Macrophages, Mice, Inbred C57BL, Milk Proteins, Phosphatidylserines, Reticulocytes, Spleen, Erythroid Precursor Cells, Apoptosis, Phlebotomy, Mice

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