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Phagocytosis of necrotic cells by macrophages is phosphatidylserine dependent and does not induce inflammatory cytokine production

Greet Brouckaert, Michaël Kalai, Dmitri Krysko UGent, Xavier Saelens UGent, Dominique Vercammen, Matladi Ndlovu, Guy Haegeman UGent, Katharina D'Herde UGent and Peter Vandenabeele UGent (2004) MOLECULAR BIOLOGY OF THE CELL. 15(3). p.1089-1100
abstract
Apoptotic cells are cleared by phagocytosis during development, homeostasis, and pathology. However, it is still unclear how necrotic cells are removed. We compared the phagocytic uptake by macrophages of variants of L929sA murine fibrosarcoma cells induced to die by tumor necrosis factor-induced necrosis or by Fas-mediated apoptosis. We show that apoptotic and necrotic cells are recognized and phagocytosed by macrophages, whereas living cells are not. In both cases, phagocytosis occurred through a phosphatidylserine-dependent mechanism, suggesting that externalization of phosphatidylserine is a general trigger for clearance by macrophages. However, uptake of apoptotic cells was more efficient both quantitatively and kinetically than phagocytosis of necrotic cells. Electron microscopy showed clear morphological differences in the mechanisms used by macrophages to engulf necrotic and apoptotic cells. Apoptotic cells were taken up as condensed membrane-bound particles of various sizes rather than as whole cells, whereas necrotic cells were internalized only as small cellular particles after loss of membrane integrity. Uptake of neither apoptotic nor necrotic L929 cells by macrophages modulated the expression of proinflammatory cytokines by the phagocytes.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
MECHANISMS, CLEARANCE, L929 CELLS, FAS RECEPTOR, DEATH PATHWAY, DOWN-REGULATION, DENDRITIC CELLS, APOPTOTIC CELLS, FACTOR-INDUCED NECROSIS, EXPOSURE
journal title
MOLECULAR BIOLOGY OF THE CELL
Mol. Biol. Cell
volume
15
issue
3
pages
1089 - 1100
Web of Science type
Article
Web of Science id
000220051900015
JCR category
CELL BIOLOGY
JCR impact factor
7.517 (2004)
JCR rank
20/153 (2004)
JCR quartile
1 (2004)
ISSN
1059-1524
DOI
10.1091/mbc.E03-09-0668
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
210514
handle
http://hdl.handle.net/1854/LU-210514
date created
2004-04-14 10:11:00
date last changed
2012-06-26 14:30:27
@article{210514,
  abstract     = {Apoptotic cells are cleared by phagocytosis during development, homeostasis, and pathology. However, it is still unclear how necrotic cells are removed. We compared the phagocytic uptake by macrophages of variants of L929sA murine fibrosarcoma cells induced to die by tumor necrosis factor-induced necrosis or by Fas-mediated apoptosis. We show that apoptotic and necrotic cells are recognized and phagocytosed by macrophages, whereas living cells are not. In both cases, phagocytosis occurred through a phosphatidylserine-dependent mechanism, suggesting that externalization of phosphatidylserine is a general trigger for clearance by macrophages. However, uptake of apoptotic cells was more efficient both quantitatively and kinetically than phagocytosis of necrotic cells. Electron microscopy showed clear morphological differences in the mechanisms used by macrophages to engulf necrotic and apoptotic cells. Apoptotic cells were taken up as condensed membrane-bound particles of various sizes rather than as whole cells, whereas necrotic cells were internalized only as small cellular particles after loss of membrane integrity. Uptake of neither apoptotic nor necrotic L929 cells by macrophages modulated the expression of proinflammatory cytokines by the phagocytes.},
  author       = {Brouckaert, Greet and Kalai, Micha{\"e}l and Krysko, Dmitri and Saelens, Xavier and Vercammen, Dominique and Ndlovu, Matladi and Haegeman, Guy and D'Herde, Katharina and Vandenabeele, Peter},
  issn         = {1059-1524},
  journal      = {MOLECULAR BIOLOGY OF THE CELL},
  keyword      = {MECHANISMS,CLEARANCE,L929 CELLS,FAS RECEPTOR,DEATH PATHWAY,DOWN-REGULATION,DENDRITIC CELLS,APOPTOTIC CELLS,FACTOR-INDUCED NECROSIS,EXPOSURE},
  language     = {eng},
  number       = {3},
  pages        = {1089--1100},
  title        = {Phagocytosis of necrotic cells by macrophages is phosphatidylserine dependent and does not induce inflammatory cytokine production},
  url          = {http://dx.doi.org/10.1091/mbc.E03-09-0668},
  volume       = {15},
  year         = {2004},
}

Chicago
Brouckaert, Greet, Michaël Kalai, Dmitri Krysko, Xavier Saelens, Dominique Vercammen, Matladi Ndlovu, Guy Haegeman, Katharina D’Herde, and Peter Vandenabeele. 2004. “Phagocytosis of Necrotic Cells by Macrophages Is Phosphatidylserine Dependent and Does Not Induce Inflammatory Cytokine Production.” Molecular Biology of the Cell 15 (3): 1089–1100.
APA
Brouckaert, G., Kalai, M., Krysko, D., Saelens, X., Vercammen, D., Ndlovu, M., Haegeman, G., et al. (2004). Phagocytosis of necrotic cells by macrophages is phosphatidylserine dependent and does not induce inflammatory cytokine production. MOLECULAR BIOLOGY OF THE CELL, 15(3), 1089–1100.
Vancouver
1.
Brouckaert G, Kalai M, Krysko D, Saelens X, Vercammen D, Ndlovu M, et al. Phagocytosis of necrotic cells by macrophages is phosphatidylserine dependent and does not induce inflammatory cytokine production. MOLECULAR BIOLOGY OF THE CELL. 2004;15(3):1089–100.
MLA
Brouckaert, Greet, Michaël Kalai, Dmitri Krysko, et al. “Phagocytosis of Necrotic Cells by Macrophages Is Phosphatidylserine Dependent and Does Not Induce Inflammatory Cytokine Production.” MOLECULAR BIOLOGY OF THE CELL 15.3 (2004): 1089–1100. Print.