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A receptor for phosphatidylserine-specific clearance of apoptotic cells

Author

Listed:
  • Valerie A. Fadok

    (National Jewish Medical and Research Center)

  • Donna L. Bratton

    (National Jewish Medical and Research Center)

  • David M. Rose

    (National Jewish Medical and Research Center)

  • Alan Pearson

    (Massachusetts General Hospital)

  • R. Alan B. Ezekewitz

    (Massachusetts General Hospital)

  • Peter M. Henson

    (National Jewish Medical and Research Center)

Abstract

The culmination of apoptosis in vivo is phagocytosis of cellular corpses. During apoptosis, the asymmetry of plasma membrane phospholipids is lost, which exposes phosphatidylserine externally1,2,3,4. The phagocytosis of apoptotic cells can be inhibited stereospecifically by phosphatidylserine and its structural analogues, but not by other anionic phospholipids, suggesting that phosphatidylserine is specifically recognized1,5,6,7,8,9,10. Using phage display, we have cloned a gene that appears to recognize phosphatidylserine on apoptotic cells. Here we show that this gene, when transfected into B and T lymphocytes, enables them to recognize and engulf apoptotic cells in a phosphatidylserine-specific manner. Flow cytometric analysis using a monoclonal antibody suggested that the protein is expressed on the surface of macrophages, fibroblasts and epithelial cells; this antibody, like phosphatidylserine liposomes, inhibited the phagocytosis of apoptotic cells and, in macrophages, induced an anti-inflammatory state. This candidate phosphatidylserine receptor is highly homologous to genes of unknown function in Caenorhabditis elegans and Drosophila melanogaster, suggesting that phosphatidylserine recognition on apoptotic cells during their removal by phagocytes is highly conserved throughout phylogeny.

Suggested Citation

  • Valerie A. Fadok & Donna L. Bratton & David M. Rose & Alan Pearson & R. Alan B. Ezekewitz & Peter M. Henson, 2000. "A receptor for phosphatidylserine-specific clearance of apoptotic cells," Nature, Nature, vol. 405(6782), pages 85-90, May.
    • Handle: RePEc:nat:nature:v:405:y:2000:i:6782:d:10.1038_35011084
    DOI: 10.1038/35011084
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    Cited by:

    1. Danielle S. Potter & Ruochen Du & Stephan R. Bohl & Kin-Hoe Chow & Keith L. Ligon & Raphael Bueno & Anthony Letai, 2023. "Dynamic BH3 profiling identifies pro-apoptotic drug combinations for the treatment of malignant pleural mesothelioma," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    2. Bartosz Wiernicki & Sophia Maschalidi & Jonathan Pinney & Sandy Adjemian & Tom Vanden Berghe & Kodi S. Ravichandran & Peter Vandenabeele, 2022. "Cancer cells dying from ferroptosis impede dendritic cell-mediated anti-tumor immunity," Nature Communications, Nature, vol. 13(1), pages 1-15, December.

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