Calreticulin Release at an Early Stage of Death Modulates the Clearance by Macrophages of Apoptotic Cells
| Autor: | Jean-Philippe Kleman, Rim Osman, Philippe Frachet, Arnaud Millet, Pascale Tacnet-Delorme |
|---|---|
| Přispěvatelé: | Institut de biologie structurale (IBS - UMR 5075 ), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Immunity and Cancer INSERM U1205, Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), ANR-16-CE11-0019,C1qEffero,C1q et efferocytose: des mécanismes moléculaires et cellulaires à la tolérance au soi ou l'autoimmunité(2016), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
lcsh:Immunologic diseases. Allergy genetic structures CD14 media_common.quotation_subject macrophage polarization Immunology Macrophage polarization Biology calreticulin 03 medical and health sciences Immune system Downregulation and upregulation Immunology and Allergy cardiovascular diseases Efferocytosis Internalization C1q media_common Original Research efferocytosis CD40 [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry Molecular Biology/Structural Biology [q-bio.BM] apoptotic cells Cell biology 030104 developmental biology biology.protein lcsh:RC581-607 Calreticulin |
| Zdroj: | Frontiers in Immunology Frontiers in Immunology, 2017, 8, pp.1034. ⟨10.3389/fimmu.2017.01034⟩ Frontiers in Immunology, Frontiers, 2017, 8, pp.1034. ⟨10.3389/fimmu.2017.01034⟩ Frontiers in Immunology, Vol 8 (2017) |
| ISSN: | 1664-3224 |
| Popis: | International audience; Calreticulin (CRT) is a well-known "eat-me" signal harbored by dying cells participating in their recognition by phagocytes. CRT is also recognized to deeply impact the immune response to altered self-cells. In this study, we focus on the role of the newly exposed CRT following cell death induction. We show that if CRT increases at the outer face of the plasma membrane and is well recognized by C1q even when phosphatidylserine is not yet detected, CRT is also released in the surrounding milieu and is able to interact with phagocytes. We observed that exogenous CRT is endocytosed by THP1 macrophages through macropinocytosis and that internalization is associated with a particular phenotype characterized by an increase of cell spreading and migration, an upregulation of CD14, an increase of interleukin-8 release, and a decrease of early apoptotic cell uptake. Importantly, CRT-induced pro-inflammatory phenotype was confirmed on human monocytes-derived macrophages by the overexpression of CD40 and CD274, and we found that monocyte-derived macrophages exposed to CRT display a peculiar polarization notably associated with a downregulation of the histocompatibility complex of class II molecules hampering its description through the classical M1/M2 dichotomy. Altogether our results highlight the role of soluble CRT with strong possible consequences on the macrophage-mediated immune response to dying cell. |
| Databáze: | OpenAIRE |
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