Neuronal apoptotic bodies: phagocytosis and degradation by primary microglial cells.
Neuronal loss via apoptosis is a key element in numerous neurodegenerative diseases. To avoid accumulation of apoptotic material, the remains of apoptotic cells should be degraded. It was suggested that microglial cells are phagocytosing and degrading apoptotic material. There is only limited information available concerning the fate of the remains of apoptotic neurons. In this study, we investigated the ability of microglial cells to take up and degrade neuronal apoptotic material. We isolated primary microglial cells and used apoptotic bodies of apoptotic neuron-like PC12 cells as a substrate. The apoptotic material was taken up and degraded within the microglial cells. The uptake is clearly activation dependent. We were able to demonstrate that the CD36 scavenger receptor is involved in the uptake of the apoptotic material via competition studies, antibody blockage, and use of a CD36 mutant rat strain. Blockage of other uptake mechanisms was also able to inhibit the uptake to some extent. Furthermore, we were able to demonstrate the role of the microglial lysosomal and proteasomal pathways in the degradation of proteins originating from apoptotic bodies.
Stolzing
Alexandra
A
Neuroscience Research Center, Medical Faculty (Charité), Humboldt University, Berlin, Germany.
Grune
Tilman
T
D000818:Animals; D017209:Apoptosis; D018955:CD36 Antigens / Q000378:metabolism / Q000502:physiology; D002478:Cells, Cultured; D003546:Cysteine Endopeptidases / Q000378:metabolism; D010450:Endopeptidases / Q000378:metabolism; D008247:Lysosomes / Q000201:enzymology; D017628:Microglia / Q000378:metabolism*; D008954:Models, Biological; D009097:Multienzyme Complexes / Q000378:metabolism; D009474:Neurons / Q000166:cytology*; D016716:PC12 Cells; D010587:Phagocytosis; D046988:Proteasome Endopeptidase Complex; D011506:Proteins / Q000378:metabolism; D051381:Rats
D018955:CD36 Antigens; D009097:Multienzyme Complexes; D011506:Proteins; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex