The synthetic phospholipid C8-C1P determines pro-angiogenic and pro-reparative features in human macrophages restraining the proinflammatory M1-like phenotype
Monocytes (Mo) are highly plastic myeloid cells that differentiate into macrophages after extravasation, playing a pivotal role in the resolution of inflammation and regeneration of injured tissues. Wound-infiltrated monocytes/macrophages are more pro-inflammatory at early time points, while showing...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-06-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1162671/full |
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| author | Juan Manuel Ortiz Wilczyñski Hebe Agustina Mena Martin Manuel Ledesma Cinthia Mariel Olexen Cinthia Mariel Olexen Enrique Podaza Mirta Schattner Soledad Negrotto Andrea Emilse Errasti Eugenio Antonio Carrera Silva |
| author_facet | Juan Manuel Ortiz Wilczyñski Hebe Agustina Mena Martin Manuel Ledesma Cinthia Mariel Olexen Cinthia Mariel Olexen Enrique Podaza Mirta Schattner Soledad Negrotto Andrea Emilse Errasti Eugenio Antonio Carrera Silva |
| author_sort | Juan Manuel Ortiz Wilczyñski |
| collection | DOAJ |
| description | Monocytes (Mo) are highly plastic myeloid cells that differentiate into macrophages after extravasation, playing a pivotal role in the resolution of inflammation and regeneration of injured tissues. Wound-infiltrated monocytes/macrophages are more pro-inflammatory at early time points, while showing anti-inflammatory/pro-reparative phenotypes at later phases, with highly dynamic switching depending on the wound environment. Chronic wounds are often arrested in the inflammatory phase with hampered inflammatory/repair phenotype transition. Promoting the tissue repair program switching represents a promising strategy to revert chronic inflammatory wounds, one of the major public health loads. We found that the synthetic lipid C8-C1P primes human CD14+ monocytes, restraining the inflammatory activation markers (HLA-DR, CD44, and CD80) and IL-6 when challenged with LPS, and preventing apoptosis by inducing BCL-2. We also observed increased pseudo-tubule formation of human endothelial-colony-forming cells (ECFCs) when stimulated with the C1P-macrophages secretome. Moreover, C8-C1P-primed monocytes skew differentiation toward pro-resolutive-like macrophages, even in the presence of inflammatory PAMPs and DAMPs by increasing anti-inflammatory and pro-angiogenic gene expression patterns. All these results indicate that C8-C1P could restrain M1 skewing and promote the program of tissue repair and pro-angiogenic macrophage. |
| first_indexed | 2024-03-13T05:12:42Z |
| format | Article |
| id | doaj.art-16aab086a94c4d6e86d014d074c5b11f |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-13T05:12:42Z |
| publishDate | 2023-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-16aab086a94c4d6e86d014d074c5b11f2023-06-16T04:45:46ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-06-011410.3389/fimmu.2023.11626711162671The synthetic phospholipid C8-C1P determines pro-angiogenic and pro-reparative features in human macrophages restraining the proinflammatory M1-like phenotypeJuan Manuel Ortiz Wilczyñski0Hebe Agustina Mena1Martin Manuel Ledesma2Cinthia Mariel Olexen3Cinthia Mariel Olexen4Enrique Podaza5Mirta Schattner6Soledad Negrotto7Andrea Emilse Errasti8Eugenio Antonio Carrera Silva9Institute of Experimental Medicine, National Scientific and Technological Research Council - National Academy of Medicine (IMEX-CONICET-ANM), Buenos Aires, ArgentinaInstitute of Experimental Medicine, National Scientific and Technological Research Council - National Academy of Medicine (IMEX-CONICET-ANM), Buenos Aires, ArgentinaInstitute of Experimental Medicine, National Scientific and Technological Research Council - National Academy of Medicine (IMEX-CONICET-ANM), Buenos Aires, ArgentinaInstitute of Experimental Medicine, National Scientific and Technological Research Council - National Academy of Medicine (IMEX-CONICET-ANM), Buenos Aires, ArgentinaInstitute of Pharmacology, School of Medicine, University of Buenos Aires, Buenos Aires, ArgentinaCaryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, United StatesInstitute of Experimental Medicine, National Scientific and Technological Research Council - National Academy of Medicine (IMEX-CONICET-ANM), Buenos Aires, ArgentinaInstitute of Experimental Medicine, National Scientific and Technological Research Council - National Academy of Medicine (IMEX-CONICET-ANM), Buenos Aires, ArgentinaInstitute of Pharmacology, School of Medicine, University of Buenos Aires, Buenos Aires, ArgentinaInstitute of Experimental Medicine, National Scientific and Technological Research Council - National Academy of Medicine (IMEX-CONICET-ANM), Buenos Aires, ArgentinaMonocytes (Mo) are highly plastic myeloid cells that differentiate into macrophages after extravasation, playing a pivotal role in the resolution of inflammation and regeneration of injured tissues. Wound-infiltrated monocytes/macrophages are more pro-inflammatory at early time points, while showing anti-inflammatory/pro-reparative phenotypes at later phases, with highly dynamic switching depending on the wound environment. Chronic wounds are often arrested in the inflammatory phase with hampered inflammatory/repair phenotype transition. Promoting the tissue repair program switching represents a promising strategy to revert chronic inflammatory wounds, one of the major public health loads. We found that the synthetic lipid C8-C1P primes human CD14+ monocytes, restraining the inflammatory activation markers (HLA-DR, CD44, and CD80) and IL-6 when challenged with LPS, and preventing apoptosis by inducing BCL-2. We also observed increased pseudo-tubule formation of human endothelial-colony-forming cells (ECFCs) when stimulated with the C1P-macrophages secretome. Moreover, C8-C1P-primed monocytes skew differentiation toward pro-resolutive-like macrophages, even in the presence of inflammatory PAMPs and DAMPs by increasing anti-inflammatory and pro-angiogenic gene expression patterns. All these results indicate that C8-C1P could restrain M1 skewing and promote the program of tissue repair and pro-angiogenic macrophage.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1162671/fullceramide 1-phosphatemacrophagesinflammationtissue repairangiogenesis |
| spellingShingle | Juan Manuel Ortiz Wilczyñski Hebe Agustina Mena Martin Manuel Ledesma Cinthia Mariel Olexen Cinthia Mariel Olexen Enrique Podaza Mirta Schattner Soledad Negrotto Andrea Emilse Errasti Eugenio Antonio Carrera Silva The synthetic phospholipid C8-C1P determines pro-angiogenic and pro-reparative features in human macrophages restraining the proinflammatory M1-like phenotype Frontiers in Immunology ceramide 1-phosphate macrophages inflammation tissue repair angiogenesis |
| title | The synthetic phospholipid C8-C1P determines pro-angiogenic and pro-reparative features in human macrophages restraining the proinflammatory M1-like phenotype |
| title_full | The synthetic phospholipid C8-C1P determines pro-angiogenic and pro-reparative features in human macrophages restraining the proinflammatory M1-like phenotype |
| title_fullStr | The synthetic phospholipid C8-C1P determines pro-angiogenic and pro-reparative features in human macrophages restraining the proinflammatory M1-like phenotype |
| title_full_unstemmed | The synthetic phospholipid C8-C1P determines pro-angiogenic and pro-reparative features in human macrophages restraining the proinflammatory M1-like phenotype |
| title_short | The synthetic phospholipid C8-C1P determines pro-angiogenic and pro-reparative features in human macrophages restraining the proinflammatory M1-like phenotype |
| title_sort | synthetic phospholipid c8 c1p determines pro angiogenic and pro reparative features in human macrophages restraining the proinflammatory m1 like phenotype |
| topic | ceramide 1-phosphate macrophages inflammation tissue repair angiogenesis |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1162671/full |
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