Macrophage expression of LRP1, a receptor for apoptotic cells and unopsonized erythrocytes, can be regulated by glucocorticoids
► Dexamethasone increases cell surface levels of LRP1 in primary murine macrophages. ► This effect is seen already at 10nM dexamethasone. ► The LRP1 upregulation enhances LRP1-mediated phagocytosis of target host cells. Macrophage phagocytosis of apoptotic cells, or unopsonized viable CD47−/− red bl...
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Published in | Biochemical and biophysical research communications Vol. 417; no. 4; pp. 1304 - 1309 |
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Main Authors | , , |
Format | Journal Article |
Language | English |
Published |
United States
Elsevier Inc
27.01.2012
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Subjects | |
Online Access | Get full text |
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Summary: | ► Dexamethasone increases cell surface levels of LRP1 in primary murine macrophages. ► This effect is seen already at 10nM dexamethasone. ► The LRP1 upregulation enhances LRP1-mediated phagocytosis of target host cells.
Macrophage phagocytosis of apoptotic cells, or unopsonized viable CD47−/− red blood cells, can be mediated by the interaction between calreticulin (CRT) on the target cell and LDL receptor-related protein-1 (LRP1/CD91/α2-macroglobulin receptor) on the macrophage. Glucocorticoids (GC) are powerful in treatment of a range of inflammatory conditions, and were shown to enhance macrophage uptake of apoptotic cells. Here we investigated if the ability of GC to promote macrophage uptake of apoptotic cells could in part be mediated by an upregulation of macrophage LRP1 expression. Using both resident peritoneal and bone marrow-derived macrophages, we found that the GC dexamethasone could dose- and time-dependently increase macrophage LRP1 expression. The GC receptor–inhibitor RU486 could dose-dependently prevent LRP1 upregulation. Dexamethasone-treated macrophages did also show enhanced phagocytosis of apoptotic thymocytes as well as unopsonized viable CD47−/− red blood cells, which was sensitive to inhibition by the LRP1-agonist RAP. In conclusion, these data suggest that GC-stimulated macrophage uptake of apoptotic cells may involve an upregulation of macrophage LRP1 expression and enhanced LRP1-mediated phagocytosis. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0006-291X 1090-2104 1090-2104 |
DOI: | 10.1016/j.bbrc.2011.12.137 |