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A more recent version of this article appeared on March 1, 2004
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Submitted on September 16, 2003
Revised on November 25, 2003
Accepted on November 25, 2003
1 Molecular Signalling and Cell Death Unit, Department of Molecular Biomedical Research, VIB, Ghent University, Belgium
2 Molecular Signalling and Cell Death Unit, Department of Molecular Biomedical Research, VIB, Ghent University, Belgium, Both authors share senior authorship
3 Department of Human Anatomy, Embryology, Histology and Medical Physics, Ghent University, Belgium
4 Molecular Signalling and Cell Death Unit, Department of Molecular Biomedical Research, VIB, Ghent University, Belgium; Current address: Department of Plant System Biology, VIB, Ghent University, Belgium
5 Laboratory of Eukaryotic Gene Expression and Signal Transduction, Department of Molecular Biology, Ghent University, Belgium
6 Molecular Signalling and Cell Death Unit, Department of Molecular Biomedical Research, VIB, Ghent University, Belgium; Technologiepark 927, B-9052, Zwijnaarde Belgium, Both authors share senior authorship
* Corresponding author. E-mail address: peter.vandenabeele{at}dmbr.UGent.be.
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 TNF-induced necrosis or by Fas-mediated apoptosis. We show that apoptotic and necrotic cells are recognized and phagocytosed by macrophages, while 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, while necrotic cells were internalized only as small cellular particles following loss of membrane integrity. Uptake of neither apoptotic nor necrotic L929 cells by macrophages modulated the expression of proinflammatory cytokines by the phagocytes.
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