The phagocytic capacity of neurones

Abstract

Phagocytosis is defined as the ingestion of particulates over 0.5 microm in diameter and is associated with cells of the immune system such as macrophages or monocytes. Neurones are not generally recognized to be phagocytic. Using light, confocal, time-lapse and electron microscopy, we carried out a wide range of in-vitro and in-vivo experiments to examine the phagocytic capacity of different neuronal cell types. We demonstrated phagocytosis of material by neurones, including cell debris and synthetic particles up to 2.8 microm in diameter. We showed phagocytosis in different neuronal types, and demonstrated that debris can be transported from neurite extremities to cell bodies and persist within neurones. Flow cytometry analysis demonstrated the lack of certain complement receptors on neurones but the presence of others, including integrin receptors known to mediate macrophage phagocytosis, indicating that a restricted set of phagocytosis receptors may mediate this process. Neuronal phagocytosis occurs in vitro and in vivo, and we propose that this is a more widespread and significant process than previously recognized. Neuronal phagocytosis may explain certain inclusions in neurones during disease, cell-to-cell spread of disease, neuronal death during disease progression and provide a potential mechanism for therapeutic intervention through the delivery of particulate drug carriers.

Cellular markers of neuroinflammation and neurogenesis after ischemic brain injury in the long-term survival rat model

“…It may, however, seem unusual to assume a phagocytosis-like fusion role of neurons toward microglia. Nevertheless, different phagocytotic manifestations were observed in neurons (Bowen et al 2007), and interestingly, traces of apoptotic T cells were also found inside the perikaryon of facial motor neurons (Flügel et al 2000). In addition, unlike OX42-positive microglia, in the present study ED1-positive macrophages were not easily identified.…”

Vacuolar Protein Sorting Protein 13A, TtVPS13A, Localizes to the Tetrahymena thermophila Phagosome Membrane and Is Required for Efficient Phagocytosis

“…A partial defect in RBC phagocytosis might lead to older cells with membrane defects in the circulation. In the brain, microglia are the major phagocytic cells, but neurons have also been reported to carry out phagocytosis (4). While the mechanism is not yet entirely clear, microglia have been implicated in neuronal loss in a number of neurodegenerative disorders (reviewed in reference 33), raising the possibility that a partial defect in microglial phagocytosis might be responsible for the brain pathology observed for chorea-acanthocytosis.…”

P2X7 Receptor-mediated Scavenger Activity of Mononuclear Phagocytes toward Non-opsonized Particles and Apoptotic Cells Is Inhibited by Serum Glycoproteins but Remains Active in Cerebrospinal Fluid

“…The highest expression of P2X7 receptors is on professional phagocytes of monocyte/macrophage lineage including microglia (10), but P2X7 also has ubiquitous distribution, and other cell types (e.g. epithelial and both mature and progenitor neuronal cells) are able to recognize and engulf apoptotic cells at slower rates (11)(12)(13). Apart from certain complement components (14), physiological regulators in the process of non-inflammatory removal of apoptotic cells have yet to be identified.…”