Phagocytosis of Erythrocytes from Gaucher Patients Induces Phenotypic Modifications in Macrophages, Driving Them toward Gaucher Cells
Gaucher disease (GD) is caused by glucocerebrosidase deficiency leading to the accumulation of sphingolipids in macrophages named “Gaucher’s Cells”. These cells are characterized by deregulated expression of cell surface markers, abnormal secretion of inflammatory cytokines, and iron sequestration....
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MDPI AG
2022-07-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/14/7640 |
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| author | Lucie Dupuis Margaux Chauvet Emmanuelle Bourdelier Michaël Dussiot Nadia Belmatoug Caroline Le Van Kim Arnaud Chêne Mélanie Franco |
| author_facet | Lucie Dupuis Margaux Chauvet Emmanuelle Bourdelier Michaël Dussiot Nadia Belmatoug Caroline Le Van Kim Arnaud Chêne Mélanie Franco |
| author_sort | Lucie Dupuis |
| collection | DOAJ |
| description | Gaucher disease (GD) is caused by glucocerebrosidase deficiency leading to the accumulation of sphingolipids in macrophages named “Gaucher’s Cells”. These cells are characterized by deregulated expression of cell surface markers, abnormal secretion of inflammatory cytokines, and iron sequestration. These cells are known to infiltrate tissues resulting in hematological manifestations, splenomegaly, and bone diseases. We have already demonstrated that Gaucher red blood cells exhibit altered properties suggesting their key role in GD clinical manifestations. We hypothesized that Gaucher’s erythrocytes could be prone to premature destruction by macrophages contributing to the formation of altered macrophages and Gaucher-like cells. We conducted in vitro experiments of erythrophagocytosis using erythrocytes from Gaucher’s patients or healthy donors. Our results showed an enhanced erythrophagocytosis of Gaucher red blood cells compared to healthy red blood cells, which is related to erythrocyte sphingolipids overload and reduced deformability. Importantly, we showed elevated expression of the antigen-presenting molecules CD1d and MHC-II and of the iron-regulator hepcidin in macrophages, as well as enhanced secretion of the pro-inflammatory cytokine IL-1β after phagocytosis of GD erythrocytes. These results strongly suggested that erythrophagocytosis in GD contribute to phenotypic modifications in macrophages. This present study shows that erythrocytes-macrophages interactions may be crucial in GD pathophysiology and pathogenesis. |
| first_indexed | 2024-03-09T13:43:40Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T13:43:40Z |
| publishDate | 2022-07-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-d40cf1732b7f44ef9d97361a8feb6f052023-11-30T21:04:25ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-07-012314764010.3390/ijms23147640Phagocytosis of Erythrocytes from Gaucher Patients Induces Phenotypic Modifications in Macrophages, Driving Them toward Gaucher CellsLucie Dupuis0Margaux Chauvet1Emmanuelle Bourdelier2Michaël Dussiot3Nadia Belmatoug4Caroline Le Van Kim5Arnaud Chêne6Mélanie Franco7INSERM, UMR_S1134, BIGR, Université Paris Cité and Université des Antilles, F-75015 Paris, FranceINSERM, UMR_S1134, BIGR, Université Paris Cité and Université des Antilles, F-75015 Paris, FranceINSERM, UMR_S1134, BIGR, Université Paris Cité and Université des Antilles, F-75015 Paris, FranceUMR_S1163, Sorbonne Paris Cité, Institut Imagine, Laboratoire d’Excellence GR-Ex, Université Paris Cité, F-75015 Paris, FranceAPHP CRML Maladies Lysosomales, Service de Médecine Interne, Hôpital Beaujon, Sorbonne Université, F-92110 Clichy, FranceINSERM, UMR_S1134, BIGR, Université Paris Cité and Université des Antilles, F-75015 Paris, FranceINSERM, UMR_S1134, BIGR, Université Paris Cité and Université des Antilles, F-75015 Paris, FranceINSERM, UMR_S1134, BIGR, Université Paris Cité and Université des Antilles, F-75015 Paris, FranceGaucher disease (GD) is caused by glucocerebrosidase deficiency leading to the accumulation of sphingolipids in macrophages named “Gaucher’s Cells”. These cells are characterized by deregulated expression of cell surface markers, abnormal secretion of inflammatory cytokines, and iron sequestration. These cells are known to infiltrate tissues resulting in hematological manifestations, splenomegaly, and bone diseases. We have already demonstrated that Gaucher red blood cells exhibit altered properties suggesting their key role in GD clinical manifestations. We hypothesized that Gaucher’s erythrocytes could be prone to premature destruction by macrophages contributing to the formation of altered macrophages and Gaucher-like cells. We conducted in vitro experiments of erythrophagocytosis using erythrocytes from Gaucher’s patients or healthy donors. Our results showed an enhanced erythrophagocytosis of Gaucher red blood cells compared to healthy red blood cells, which is related to erythrocyte sphingolipids overload and reduced deformability. Importantly, we showed elevated expression of the antigen-presenting molecules CD1d and MHC-II and of the iron-regulator hepcidin in macrophages, as well as enhanced secretion of the pro-inflammatory cytokine IL-1β after phagocytosis of GD erythrocytes. These results strongly suggested that erythrophagocytosis in GD contribute to phenotypic modifications in macrophages. This present study shows that erythrocytes-macrophages interactions may be crucial in GD pathophysiology and pathogenesis.https://www.mdpi.com/1422-0067/23/14/7640red blood cellserythrophagocytosismacrophagesGaucher disease |
| spellingShingle | Lucie Dupuis Margaux Chauvet Emmanuelle Bourdelier Michaël Dussiot Nadia Belmatoug Caroline Le Van Kim Arnaud Chêne Mélanie Franco Phagocytosis of Erythrocytes from Gaucher Patients Induces Phenotypic Modifications in Macrophages, Driving Them toward Gaucher Cells International Journal of Molecular Sciences red blood cells erythrophagocytosis macrophages Gaucher disease |
| title | Phagocytosis of Erythrocytes from Gaucher Patients Induces Phenotypic Modifications in Macrophages, Driving Them toward Gaucher Cells |
| title_full | Phagocytosis of Erythrocytes from Gaucher Patients Induces Phenotypic Modifications in Macrophages, Driving Them toward Gaucher Cells |
| title_fullStr | Phagocytosis of Erythrocytes from Gaucher Patients Induces Phenotypic Modifications in Macrophages, Driving Them toward Gaucher Cells |
| title_full_unstemmed | Phagocytosis of Erythrocytes from Gaucher Patients Induces Phenotypic Modifications in Macrophages, Driving Them toward Gaucher Cells |
| title_short | Phagocytosis of Erythrocytes from Gaucher Patients Induces Phenotypic Modifications in Macrophages, Driving Them toward Gaucher Cells |
| title_sort | phagocytosis of erythrocytes from gaucher patients induces phenotypic modifications in macrophages driving them toward gaucher cells |
| topic | red blood cells erythrophagocytosis macrophages Gaucher disease |
| url | https://www.mdpi.com/1422-0067/23/14/7640 |
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