Phagocyte Chemoattraction Is Induced through the Mcp-1–Ccr2 Axis during Efferocytosis
Apoptotic cells generated during development and for tissue homeostasis are swiftly and continuously removed by phagocytes via a process called efferocytosis. Efficient efferocytosis can be achieved via transcriptional modulation in phagocytes that have engulfed apoptotic cells. However, such modula...
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| Autores principales: | , , , , , , , , , |
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| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
MDPI AG
2021
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| Materias: | |
| Acceso en línea: | https://doaj.org/article/d5bb6fd7f3c9485aa7edfde081811276 |
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| Sumario: | Apoptotic cells generated during development and for tissue homeostasis are swiftly and continuously removed by phagocytes via a process called efferocytosis. Efficient efferocytosis can be achieved via transcriptional modulation in phagocytes that have engulfed apoptotic cells. However, such modulation and its effect on efferocytosis are not completely understood. Here, we report that phagocytes are recruited to apoptotic cells being cleared through the Mcp-1–Ccr2 axis, which facilitates clearance of apoptotic cells. We identified <i>Mcp-1</i> as a modulated transcript using a microarray and found that Mcp-1 secretion was augmented in phagocytes engulfing apoptotic cells. This augmented Mcp-1 secretion was impaired by blocking phagolysosomal degradation of apoptotic cells. Conditioned medium from wild type (WT) phagocytes promoted cell migration, but that from <i>Mcp-1<sup>−/−</sup></i> phagocytes did not. In addition, blockade of Ccr2, the receptor for Mcp-1, abrogated cell migration to conditioned medium from phagocytes incubated with apoptotic cells. The intrinsic efferocytosis activity of <i>Mcp-1<sup>−</sup></i><sup>/<i>−</i></sup> and <i>Ccr2<sup>−</sup></i><sup>/<i>−</i></sup> phagocytes was unaltered, but clearance of apoptotic cells was less efficient in the peritoneum of <i>Mcp-1<sup>−</sup></i><sup>/<i>−</i></sup> and <i>Ccr2<sup>−</sup></i><sup>/<i>−</i></sup> mice than in that of <i>WT</i> mice because fewer Ccr2-positive phagocytes were recruited. Taken together, our findings demonstrate a mechanism by which not only apoptotic cells but also phagocytes induce chemoattraction to recruit phagocytes to sites where apoptotic cells are cleared for efficient efferocytosis. |
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