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Mechanisms of internalization of apoptotic and necrotic L929 cells by a macrophage cell line studied by electron microscopy
Author(s) -
Krysko Dmitri V.,
Brouckaert Greet,
Kalai Michael,
Vandenabeele Peter,
D'Herde Katharina
Publication year - 2003
Publication title -
journal of morphology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.652
H-Index - 74
eISSN - 1097-4687
pISSN - 0362-2525
DOI - 10.1002/jmor.10161
Subject(s) - phagocytosis , internalization , microbiology and biotechnology , phagosome , apoptosis , biology , macrophage , necrosis , programmed cell death , cell culture , cytoplasm , ultrastructure , efferocytosis , cell , in vitro , anatomy , biochemistry , genetics
Abstract Rapid and efficient phagocytic removal of dying cells is a key feature of apoptosis. In necrotic caspase‐independent modes of death, the role and extent of phagocytosis is not well documented. To address this issue, we studied at the ultrastructural level the phagocytic response to dying cells in an in vitro phagocytosis assay with a mouse macrophage cell line (Mf4/4). As target cells, murine L929sAhFas cells were induced to die by TNFR1‐mediated necrosis or by Fas‐mediated apoptosis. Apoptotic L929sAhFas cells are taken up by complete engulfment of apoptotic bodies as single entities forming a tight‐fitting phagosome, thus resembling the “zipper”‐like mechanism of internalization. In contrast, primary and secondary necrotic cells were internalized by a macropinocytotic mechanism with formation of multiple ruffles by the ingesting macrophage. Ingestion of necrotic cellular material was invariably taking place after the integrity of the cell membrane was lost and did not occur as discrete particles, in contrast to apoptotic material that is surrounded by an intact membrane. Although nuclei of necrotic cells have been observed in the vicinity of macrophages, no uptake of necrotic nuclei was observed. The present report provides a basis for future studies aimed at discovering molecular pathways that precede these diverse mechanisms of uptake. J. Morphol. 258:336–345, 2003. © 2003 Wiley‐Liss, Inc.