Phosphatidylserine-dependent phagocytosis of apoptotic glioma cells by normal human microglia, astrocytes, and glioma cells

Grace H.F. Chang, Nicholas M. Barbaro, Russell O. Pieper

Research output: Contribution to journalArticle

75 Citations (Scopus)

Abstract

Apoptotic cells display signals that trigger phagocytic removal by macrophages or neighboring cells. To better understand the signals triggering phagocytosis of apoptotic glioma cells, and to identify the cells that might be involved in the phagocytic process, U-251 MG glioma cells were made apoptotic by etoposide (25 μg/ml) treatment and were incubated with normal human astrocytes (NHA), glioma cells, or microglia. Extent of phagocytosis was assessed by an in vitro phagocytosis assay. After 3 h of incubation with apoptotic cells, phagocytes tested were washed to remove nonengulfed cells, then fixed, stained, and counted to determine phagocytosis index (PI). NHA, glioma cells, and microglia all phagocytosed apoptotic, but not nonapoptotic, glioma cells. Microglia, however, had a PI approximately 4-fold higher than did either NHA or glioma cells. Binding of phosphatidylserine (PS) on apoptotic glioma cell membranes by annexin-V inhibited phagocytosis by 90% in both microglia and NHA. The activity of an enzyme (scramblase) that moves PS from the inner cell membrane to the outer cell membrane was also increased in apoptotic glioma cells. These results suggest that a variety of cells present in and near gliomas in vivo can remove glioma cells in a PS-dependent scramblase-mediated fashion. Manipulation of scramblase and/or PS exposure in glioma cells may therefore be a means of triggering phagocytic removal of glioma cells.

Original languageEnglish (US)
Pages (from-to)174-183
Number of pages10
JournalNeuro-Oncology
Volume2
Issue number3
StatePublished - Jul 1 2000

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Phosphatidylserines
Microglia
Phagocytosis
Glioma
Astrocytes
Cell Membrane
Annexin A5
Etoposide
Phagocytes

ASJC Scopus subject areas

  • Oncology
  • Clinical Neurology
  • Cancer Research

Cite this

Phosphatidylserine-dependent phagocytosis of apoptotic glioma cells by normal human microglia, astrocytes, and glioma cells. / Chang, Grace H.F.; Barbaro, Nicholas M.; Pieper, Russell O.

In: Neuro-Oncology, Vol. 2, No. 3, 01.07.2000, p. 174-183.

Research output: Contribution to journalArticle

Chang, Grace H.F. ; Barbaro, Nicholas M. ; Pieper, Russell O. / Phosphatidylserine-dependent phagocytosis of apoptotic glioma cells by normal human microglia, astrocytes, and glioma cells. In: Neuro-Oncology. 2000 ; Vol. 2, No. 3. pp. 174-183.
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