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Apoptosis

, Volume 13, Issue 4, pp 463–482 | Cite as

Secondary necrosis in multicellular animals: an outcome of apoptosis with pathogenic implications

  • Manuel T. SilvaEmail author
  • Ana do Vale
  • Nuno M. N. dos Santos
Original Paper

Abstract

In metazoans apoptosis is a major physiological process of cell elimination during development and in tissue homeostasis and can be involved in pathological situations. In vitro, apoptosis proceeds through an execution phase during which cell dismantling is initiated, with or without fragmentation into apoptotic bodies, but with maintenance of a near-to-intact cytoplasmic membrane, followed by a transition to a necrotic cell elimination traditionally called “secondary necrosis”. Secondary necrosis involves activation of self-hydrolytic enzymes, and swelling of the cell or of the apoptotic bodies, generalized and irreparable damage to the cytoplasmic membrane, and culminates with cell disruption. In vivo, under normal conditions, the elimination of apoptosing cells or apoptotic bodies is by removal through engulfment by scavengers prompted by the exposure of engulfment signals during the execution phase of apoptosis; if this removal fails progression to secondary necrosis ensues as in the in vitro situation. In vivo secondary necrosis occurs when massive apoptosis overwhelms the available scavenging capacity, or when the scavenger mechanism is directly impaired, and may result in leakage of the cell contents with induction of tissue injury and inflammatory and autoimmune responses. Several disorders where secondary necrosis has been implicated as a pathogenic mechanism will be reviewed.

Keywords

Apoptotic secondary necrosis Apoptosis Necrosis Clearance Autoimmunity Infection 

Notes

Acknowledgements

We are grateful to Drs. Andrew H. Wyllie, Richard A. Lockshin, Luisa Minghetti, Ágnes Enyedi, David S. Pisetsky, Yasunobu Okada and in particular L. Felipe Barros for helpful discussions, to Drs. Frank Madeo, Paula Ludovico and Manuela Côrte-Real for helpful discussions and for reviewing the text and to Anabela Costa for editorial assistance. This work was supported by FCT project POCI/MAR/56111/2004 funded by POCI 2010 and co-funded by FEDER, and grant SFRH/BPD/26816/2006.

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Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Manuel T. Silva
    • 1
    Email author
  • Ana do Vale
    • 1
  • Nuno M. N. dos Santos
    • 1
  1. 1.Fish Immunology and Vaccinology, IBMC-Instituto de Biologia Molecular e CelularUniversidade do PortoPortoPortugal

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