title: Macrophage expression of LRP1, a receptor for apoptotic cells and unopsonized erythrocytes, can be regulated by glucocorticoids.
abstract: 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.
authors.affiliation: Department of Integrative Medical Biology, Section for Histology and Cell Biology, Umeå University, Umeå, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Nilsson
authors.forename: Liselotte
authors.initials: L
authors.lastname: Vesterlund
authors.forename: Per-Arne
authors.initials: PA
authors.lastname: Oldenborg
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D051928:CD47 Antigen / Q000276:immunology; D003907:Dexamethasone / Q000494:pharmacology; D004912:Erythrocytes / Q000276:immunology; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D026563:LDL-Receptor Related Protein-Associated Protein / Q000276:immunology / Q000494:pharmacology; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D015735:Mifepristone / Q000494:pharmacology; D010587:Phagocytosis / Q000235:genetics / Q000276:immunology*; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors / Q000276:immunology; D011973:Receptors, LDL / Q000819:agonists / Q000096:biosynthesis*; D025521:Tumor Suppressor Proteins / Q000819:agonists / Q000096:biosynthesis*
chemical_list: D051928:CD47 Antigen; C497894:CD47 protein, human; D005938:Glucocorticoids; D026563:LDL-Receptor Related Protein-Associated Protein; D026503:Low Density Lipoprotein Receptor-Related Protein-1; C486645:Lrp1 protein, mouse; D011965:Receptors, Glucocorticoid; D011973:Receptors, LDL; D025521:Tumor Suppressor Proteins; D015735:Mifepristone; D003907:Dexamethasone