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Enhancement of phagocytotic activity by prion protein in PrP-deficient macrophage cells
Ryuta Uraki1, Akikazu Sakudo, Saeko Ando
1Department of Molecular Immunology, School of Agricultural and Life Sciences, University of Tokyo, Bunkyo-ku Yayoi, Tokyo, Japan.
Abstract:
Macrophages, especially follicular dendritic cells, contribute to the pathogenesis of prion diseases by accumulating an abnormal isoform of prion protein (PrPSc), which is converted from the cellular isoform of prion protein (PrPC). As information on the function of PrPC in macrophages is limited, we have established a prion protein (PrP) gene (Prnp)-deficient macrophage cell line from the bone marrow of ZrchI Prnp-/- mice. These cells expressed macrophage specific proteins (F4/80 and MOMA-2) and displayed phagocytotic properties. The Prnp-/- macrophage cell line (MplZ) showed shorter pseudopodium extension and less phagocytotic activity than a Prnp+/+ macrophage cell line (MWF). In addition, the MplZ cells were more sensitive to serum deprivation than the MWF cells and underwent apoptotic cell death in these conditions. These findings suggest that PrPC enhances the incorporation of materials possibly including PrPSc and decreases the sensitivity of cells to oxidative stress, which may be induced by PrPSc accumulation.
Insights
Cellular prion protein (PrPC) in macrophages enhances material uptake and reduces cell death from stress. PrPC deficiency impairs macrophage function and increases susceptibility to apoptosis.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Macrophages, particularly follicular dendritic cells, are implicated in prion disease pathogenesis.
- Accumulation of abnormal prion protein (PrPSc) in macrophages is a key feature of prion diseases.
- The specific role of cellular prion protein (PrPC) in macrophage function remains largely unelucidated.
Purpose of the Study:
- To investigate the function of PrPC in macrophages.
- To establish and characterize a prion protein gene (Prnp)-deficient macrophage cell line.
- To compare the functional properties of Prnp-deficient macrophages with wild-type counterparts.
Main Methods:
- Generation of a Prnp-/- macrophage cell line (MplZ) from ZrchI Prnp-/- mouse bone marrow.
- Characterization of MplZ cells for macrophage-specific markers (F4/80, MOMA-2) and phagocytic activity.
- Comparative analysis of MplZ and Prnp+/+ macrophage cell lines (MWF) under serum deprivation and oxidative stress conditions.
Main Results:
- The Prnp-/- macrophage cell line (MplZ) expressed macrophage markers and exhibited phagocytosis.
- MplZ cells displayed reduced pseudopodium extension and phagocytic activity compared to MWF cells.
- MplZ cells showed increased sensitivity to serum deprivation, leading to apoptotic cell death, unlike MWF cells.
Conclusions:
- PrPC expression in macrophages appears to enhance the incorporation of materials, potentially including PrPSc.
- PrPC may confer resistance to oxidative stress, a condition possibly exacerbated by PrPSc accumulation.
- These findings highlight a novel role for PrPC in macrophage physiology and prion disease pathology.
