Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Commentary
  • Published:

With a little help from your friends: cells don't die alone

Nature Cell Biology volume 4, pages E139–E143 (2002)Cite this article

Phagocytes have long been known to engulf and degrade apoptotic cells. Recent studies in mammals and the nematode Caenorhabditis elegans have shed some light on the conserved molecular mechanisms involved in this process. A series of results now challenge the traditional view of phagocytes as simply scavengers, 'cleaning up' after apoptosis to prevent inflammatory responses, and hence tissue damage. Instead, they suggest that phagocytes are active in the induction and/or execution of apoptosis in target cells.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Different ways to die.
Figure 2: The molecular machinery of cell-corpse engulfment.
Figure 3: The genetic pathway of apoptosis in C. elegans.

References

  1. Savill, J. & Fadok, V. Corpse clearance defines the meaning of cell death. Nature 407, 784–788 (2000).

    Article  CAS  PubMed  Google Scholar 

  2. Conradt, B. Cell engulfment, no sooner ced than done. Dev. Cell 1, 445–447 (2001).

    Article  CAS  PubMed  Google Scholar 

  3. Hall, A. & Nobes, C. D. Rho GTPases: molecular switches that control the organization and dynamics of the actin cytoskeleton. Phil. Trans. R. Soc. Lond. B 355, 965–970 (2000).

    Article  CAS  Google Scholar 

  4. Hengartner, M. O. Apoptosis: corralling the corpses. Cell 104, 325–328 (2001).

    Article  CAS  PubMed  Google Scholar 

  5. Duffield, J. S. et al. Activated macrophages direct apoptosis and suppress mitosis of mesangial cells. J. Immunol. 164, 2110–2119 (2000).

    Article  CAS  PubMed  Google Scholar 

  6. Lang, R. A. & Bishop, J. M. Macrophages are required for cell death and tissue remodeling in the developing mouse eye. Cell 74, 453–462 (1993).

    Article  CAS  PubMed  Google Scholar 

  7. Diez-Roux, G. & Lang, R. A. Macrophages induce apoptosis in normal cells in vivo. Development 124, 3633–3638 (1997).

    CAS  PubMed  Google Scholar 

  8. Hedgecock, E. M., Sulston, J. E. & Thomson, J. N. Mutations affecting programmed cell deaths in the nematode Caenorhabditis elegans. Science 220, 1277–1279 (1983).

    Article  CAS  PubMed  Google Scholar 

  9. Sulston, J. E., Albertson, D. G. & Thomson, J. N. The Caenorhabditis elegans male: postembryonic development of nongonadal structures. Dev. Biol. 78, 542–576 (1980).

    Article  CAS  PubMed  Google Scholar 

  10. Aliprantis, A. O., Diez-Roux, G., Mulder, L. C., Zychlinsky, A. & Lang, R. A. Do macrophages kill through apoptosis? Immunol. Today 17, 573–576 (1996).

    Article  CAS  PubMed  Google Scholar 

  11. Reddien, P. W., Cameron, S. & Horvitz, H. R. Phagocytosis promotes programmed cell death in C. elegans. Nature 412, 198–202 (2001).

    Article  CAS  PubMed  Google Scholar 

  12. Muhl, H., Sandau, K., Brune, B., Briner, V. A. & Pfeilschifter, J. Nitric oxide donors induce apoptosis in glomerular mesangial cells, epithelial cells and endothelial cells. Eur. J. Pharmacol. 317, 137–149 (1996).

    Article  CAS  PubMed  Google Scholar 

  13. Chlichlia, K. et al. Caspase activation is required for nitric oxide-mediated, CD95(APO- 1/Fas)-dependent and independent apoptosis in human neoplastic lymphoid cells. Blood 91, 4311–4320 (1998).

    CAS  PubMed  Google Scholar 

  14. Brown, S. B. & Savill, J. Phagocytosis triggers macrophage release of Fas ligand and induces apoptosis of bystander leukocytes. J. Immunol. 162, 480–485 (1999).

    CAS  PubMed  Google Scholar 

  15. Metzstein, M. M., Stanfield, G. M. & Horvitz, H. R. Genetics of programmed cell death in C. elegans: past, present and future. Trends Genet. 14, 410–416 (1998).

    Article  CAS  PubMed  Google Scholar 

  16. Wu, Y. C., Stanfield, G. M. & Horvitz, H. R. NUC-1, a Caenorhabditis elegans DNase II homolog, functions in an intermediate step of DNA degradation during apoptosis. Genes Dev. 14, 536–548 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Parrish, J. et al. Mitochondrial endonuclease G is important for apoptosis in C. elegans. Nature 412, 90–94 (2001).

    Article  CAS  PubMed  Google Scholar 

  18. Hoeppner, D. J., Hengartner, M. O. & Schnabel, R. Engulfment genes cooperate with ced-3 to promote cell death in Caenorhabditis elegans. Nature 412, 202–206 (2001).

    Article  CAS  PubMed  Google Scholar 

  19. Green, D. R. & Beere, H. M. Apoptosis. Mostly dead. Nature 412, 133–135 (2001).

    Article  CAS  PubMed  Google Scholar 

  20. Ren, Y. & Savill, J. Apoptosis: the importance of being eaten. Cell Death Differ. 5, 563–568 (1998).

    Article  CAS  PubMed  Google Scholar 

  21. Diez-Roux, G., Argilla, M., Makarenkova, H., Ko, K. & Lang, R. A. Macrophages kill capillary cells in G1 phase of the cell cycle during programmed vascular regression. Development 126, 2141–2147 (1999).

    CAS  PubMed  Google Scholar 

  22. Tepass, U., Fessler, L. I., Aziz, A. & Hartenstein, V. Embryonic origin of hemocytes and their relationship to cell death in Drosophila. Development 120, 1829–1837 (1994).

    CAS  PubMed  Google Scholar 

  23. Zhou, L., Hashimi, H., Schwartz, L. M. & Nambu, J. R. Programmed cell death in the Drosophila central nervous system midline. Curr. Biol. 5, 784–790 (1995).

    Article  CAS  PubMed  Google Scholar 

  24. Franc, N. C., Heitzler, P., Ezekowitz, R. A. & White, K. Requirement for croquemort in phagocytosis of apoptotic cells in Drosophila. Science 284, 1991–1994 (1999).

    Article  CAS  PubMed  Google Scholar 

  25. Nagy, L., Tontonoz, P., Alvarez, J. G., Chen, H. & Evans, R. M. Oxidized LDL regulates macrophage gene expression through ligand activation of PPARγ. Cell 93, 229–240 (1998).

    Article  CAS  PubMed  Google Scholar 

  26. Wiegand, U. K., Corbach, S., Prescott, A. R., Savill, J. & Spruce, B. A. The trigger to cell death determines the efficiency with which dying cells are cleared by neighbours. Cell Death Differ. 8, 734–746 (2001).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The author would like to thank S. Tuck for critically reading the manuscript and members of her laboratory for stimulating discussions.

Author information

Authors and Affiliations

  1. Barbara Conradt is at the Max-Planck-Institute of Neurobiology, Am Klopferspitz 18a, Martinsried/Munich, D-82152, Germany

    Barbara Conradt

Authors
  1. Barbara Conradt
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Conradt, B. With a little help from your friends: cells don't die alone. Nat Cell Biol 4, E139–E143 (2002). https://doi.org/10.1038/ncb0602-e139

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/ncb0602-e139

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing