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:	Sang-Ah Lee, Deokhwan Kim, Chanhyuk Min, Byeongjin Moon, Juyeon Lee, Hyunji Moon, Susumin Yang, Chang Sup Lee, Gwangrog Lee, Daeho Park
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	efferocytosis apoptotic cells phagocytes migration chemoattraction Mcp-1 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/d5bb6fd7f3c9485aa7edfde081811276
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spelling	oai:doaj.org-article:d5bb6fd7f3c9485aa7edfde0818112762021-11-25T17:11:39ZPhagocyte Chemoattraction Is Induced through the Mcp-1–Ccr2 Axis during Efferocytosis10.3390/cells101131152073-4409https://doaj.org/article/d5bb6fd7f3c9485aa7edfde0818112762021-11-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/3115https://doaj.org/toc/2073-4409Apoptotic 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.Sang-Ah LeeDeokhwan KimChanhyuk MinByeongjin MoonJuyeon LeeHyunji MoonSusumin YangChang Sup LeeGwangrog LeeDaeho ParkMDPI AGarticleefferocytosisapoptotic cellsphagocytesmigrationchemoattractionMcp-1Biology (General)QH301-705.5ENCells, Vol 10, Iss 3115, p 3115 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	efferocytosis apoptotic cells phagocytes migration chemoattraction Mcp-1 Biology (General) QH301-705.5
spellingShingle	efferocytosis apoptotic cells phagocytes migration chemoattraction Mcp-1 Biology (General) QH301-705.5 Sang-Ah Lee Deokhwan Kim Chanhyuk Min Byeongjin Moon Juyeon Lee Hyunji Moon Susumin Yang Chang Sup Lee Gwangrog Lee Daeho Park Phagocyte Chemoattraction Is Induced through the Mcp-1–Ccr2 Axis during Efferocytosis
description	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.
format	article
author	Sang-Ah Lee Deokhwan Kim Chanhyuk Min Byeongjin Moon Juyeon Lee Hyunji Moon Susumin Yang Chang Sup Lee Gwangrog Lee Daeho Park
author_facet	Sang-Ah Lee Deokhwan Kim Chanhyuk Min Byeongjin Moon Juyeon Lee Hyunji Moon Susumin Yang Chang Sup Lee Gwangrog Lee Daeho Park
author_sort	Sang-Ah Lee
title	Phagocyte Chemoattraction Is Induced through the Mcp-1–Ccr2 Axis during Efferocytosis
title_short	Phagocyte Chemoattraction Is Induced through the Mcp-1–Ccr2 Axis during Efferocytosis
title_full	Phagocyte Chemoattraction Is Induced through the Mcp-1–Ccr2 Axis during Efferocytosis
title_fullStr	Phagocyte Chemoattraction Is Induced through the Mcp-1–Ccr2 Axis during Efferocytosis
title_full_unstemmed	Phagocyte Chemoattraction Is Induced through the Mcp-1–Ccr2 Axis during Efferocytosis
title_sort	phagocyte chemoattraction is induced through the mcp-1–ccr2 axis during efferocytosis
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/d5bb6fd7f3c9485aa7edfde081811276
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Phagocyte Chemoattraction Is Induced through the Mcp-1–Ccr2 Axis during Efferocytosis

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