Phagocyte Chemoattraction Is Induced through the Mcp-1–Ccr2 Axis during Efferocytosis

Cells

Chang Sup Lee¹  Byeongjin Moon²  Susumin Yang²  Chanhyuk Min²  Deokhwan Kim²  Daeho Park²  Juyeon Lee²  Hyunji Moon²  Sang-Ah Lee²  Gwangrog Lee² 

[1] College of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National University, Jinju 52828, Korea;School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 61005, Korea;

关键词: efferocytosis;    apoptotic cells;    phagocytes;    migration;    chemoattraction;    Mcp-1;   

DOI  :  10.3390/cells10113115

来源: DOAJ

【 摘 要 】

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 Mcp-1 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 Mcp-1^−/− 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 Mcp-1^−/− and Ccr2^−/− phagocytes was unaltered, but clearance of apoptotic cells was less efficient in the peritoneum of Mcp-1^−/− and Ccr2^−/− mice than in that of WT 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.

【 授权许可】

Unknown