Stolzing Alexandra, Grune Tilman
Neuroscience Research Center, Medical Faculty (Charité), Humboldt University, Berlin, Germany.
FASEB J. 2004 Apr;18(6):743-5. doi: 10.1096/fj.03-0374fje. Epub 2004 Feb 6.
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.
通过凋亡导致的神经元丢失是众多神经退行性疾病的关键因素。为避免凋亡物质的积累，凋亡细胞的残骸应被降解。有人提出小胶质细胞会吞噬并降解凋亡物质。关于凋亡神经元残骸的去向，现有信息有限。在本研究中，我们调查了小胶质细胞摄取和降解神经元凋亡物质的能力。我们分离出原代小胶质细胞，并使用凋亡的神经元样PC12细胞的凋亡小体作为底物。凋亡物质在小胶质细胞内被摄取并降解。这种摄取明显依赖于激活。通过竞争研究、抗体阻断以及使用CD36突变大鼠品系，我们能够证明CD36清道夫受体参与了凋亡物质的摄取。阻断其他摄取机制也能在一定程度上抑制摄取。此外，我们能够证明小胶质细胞的溶酶体和蛋白酶体途径在源自凋亡小体的蛋白质降解中的作用。
