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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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Autores principales: Dupuis, Lucie, Chauvet, Margaux, Bourdelier, Emmanuelle, Dussiot, Michaël, Belmatoug, Nadia, Le Van Kim, Caroline, Chêne, Arnaud, Franco, Mélanie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9319206/
https://www.ncbi.nlm.nih.gov/pubmed/35886988
http://dx.doi.org/10.3390/ijms23147640
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author Dupuis, Lucie
Chauvet, Margaux
Bourdelier, Emmanuelle
Dussiot, Michaël
Belmatoug, Nadia
Le Van Kim, Caroline
Chêne, Arnaud
Franco, Mélanie
author_facet Dupuis, Lucie
Chauvet, Margaux
Bourdelier, Emmanuelle
Dussiot, Michaël
Belmatoug, Nadia
Le Van Kim, Caroline
Chêne, Arnaud
Franco, Mélanie
author_sort Dupuis, Lucie
collection PubMed
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.
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spelling pubmed-93192062022-07-27 Phagocytosis of Erythrocytes from Gaucher Patients Induces Phenotypic Modifications in Macrophages, Driving Them toward Gaucher Cells Dupuis, Lucie Chauvet, Margaux Bourdelier, Emmanuelle Dussiot, Michaël Belmatoug, Nadia Le Van Kim, Caroline Chêne, Arnaud Franco, Mélanie Int J Mol Sci Article 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. MDPI 2022-07-11 /pmc/articles/PMC9319206/ /pubmed/35886988 http://dx.doi.org/10.3390/ijms23147640 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Dupuis, Lucie
Chauvet, Margaux
Bourdelier, Emmanuelle
Dussiot, Michaël
Belmatoug, Nadia
Le Van Kim, Caroline
Chêne, Arnaud
Franco, Mélanie
Phagocytosis of Erythrocytes from Gaucher Patients Induces Phenotypic Modifications in Macrophages, Driving Them toward Gaucher Cells
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 Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9319206/
https://www.ncbi.nlm.nih.gov/pubmed/35886988
http://dx.doi.org/10.3390/ijms23147640
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