The cellular prion protein modulates phagocytosis and inflammatory response

The cellular prion protein (PrPc) is a glycoprotein anchored by glycosylphosphatidylinositol (GPI) to the cell surface and is abundantly expressed in the central nervous system. It is also expressed in a variety of cell types of the immune system. We investigated the role of PrPc in the phagocytosis...

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Bibliographic Details
Published inJournal of leukocyte biology Vol. 77; no. 2; pp. 238 - 246
Main Authors Almeida, Cecília J. G., Chiarini, Luciana B., Silva, Juliane Pereira, Silva, Patrícia M. R., Martins, Marco Aurélio, Linden, Rafael
Format Journal Article
LanguageEnglish
Published United States Society for Leukocyte Biology 01.02.2005
Subjects
Animals
apoptosis
Apoptosis - genetics
Apoptosis - immunology
Apoptosis - physiology
Inflammation - immunology
Inflammation - metabolism
Leukocytes - physiology
macrophage
Macrophages - physiology
Mice
Mice, Inbred C57BL
Mice, Knockout
Phagocytosis - genetics
Phagocytosis - immunology
Phagocytosis - physiology
PrPc
PrPC Proteins - physiology
zymosan
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Summary:The cellular prion protein (PrPc) is a glycoprotein anchored by glycosylphosphatidylinositol (GPI) to the cell surface and is abundantly expressed in the central nervous system. It is also expressed in a variety of cell types of the immune system. We investigated the role of PrPc in the phagocytosis of apoptotic cells and other particles. Macrophages from mice with deletion of the Prnp gene showed higher rates of phagocytosis than wild‐type macrophages in in vitro assays. The elimination of GPI‐anchored proteins from the cell surface of macrophages from wild‐type mice rendered these cells as efficient as macrophages derived from knockout mice. In situ detection of phagocytosis of apoptotic bodies within the retina indicated augmented phagocytotic activity in knockout mice. In an in vivo assay of acute peritonitis, knockout mice showed more efficient phagocytosis of zymosan particles than wild‐type mice. In addition, leukocyte recruitment was altered in knockout mice, as compared with wild type. The data show that PrPc modulates phagocytosis in vitro and in vivo. This activity is described for the first time and may be important for normal macrophage functions as well as for the pathogenesis of prion diseases.
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ISSN:0741-5400
1938-3673
DOI:10.1189/jlb.1103531