Tsai Wen-Hui, Chang Shao-Chi, Lin Yu-Chieh, Hsu Hui-Chi
Department of Respiratory Therapy, Taipei Medical University, Taipei 106, Taiwan.
Department of Physiology, School of Medicine, National Yang-Ming Chiao-Tung University, Taipei 112, Taiwan.
Cells. 2021 Sep 28;10(10):2583. doi: 10.3390/cells10102583.
During the resolution phase of acute lung injury, apoptotic cells release CX3CL1 as a "find-me" signal to attract alveolar macrophage transmigration toward apoptotic cells for phagocytosis. However, it is still not clear whether CX3CL1 has pro-phagocytic activity on alveolar macrophage. In this study, we investigated the role of apoptotic NB4 cells-derived CX3CL1(+) microparticles (apo-MP) on the phagocytic activity of NR8383 cells. We demonstrate that exogenous CX3CL1 and apo-MP enhanced the phagocytic activity of NR8383 cells in a CX3 CR1-dependent manner. The apo-MP-enhanced phagocytic activity on NR8383 was attenuated when apo-MP and NR8383 cells were pre-treated with anti-CX3CL1 antibodies and anti-CX3CR1 antibody, respectively, before incubating both for phagocytic assay. Further studies demonstrate that exogenous CX3CL1 and apo-MP also enhanced NR8383 cells in their surface expression and release of MFG-E8 in a CX3CR1 dependent manner. The enhanced phagocytic activity of CX3CL1-treated NR8383 cells was attenuated when NR8383 cells were pre-treated with an anti-MFG-E8 antibody before CX3CL1 treatment. We conclude that apoptotic cell-derived CX3CL1(+) microparticles enhance the phagocytic activity of NR8383 cells by up-regulating their MFG-E8 as a bridge molecule, and these contribute to the formation of phagocytic synapses between apoptotic cells and alveolar macrophages for the subsequent phagocytic clearance of apoptotic cells.
在急性肺损伤的消退阶段，凋亡细胞释放CX3CL1作为“找到我”信号，吸引肺泡巨噬细胞向凋亡细胞迁移以进行吞噬作用。然而，CX3CL1对肺泡巨噬细胞是否具有促吞噬活性仍不清楚。在本研究中，我们调查了凋亡NB4细胞衍生的CX3CL1(+)微粒（凋亡微粒）对NR8383细胞吞噬活性的作用。我们证明外源性CX3CL1和凋亡微粒以CX3CR1依赖的方式增强了NR8383细胞的吞噬活性。在将凋亡微粒和NR8383细胞共同孵育进行吞噬试验之前，分别用抗CX3CL1抗体和抗CX3CR1抗体对凋亡微粒和NR8383细胞进行预处理，凋亡微粒增强的NR8383细胞吞噬活性减弱。进一步研究表明，外源性CX3CL1和凋亡微粒还以CX3CR1依赖的方式增强了NR8383细胞表面MFG-E8的表达和释放。在用CX3CL1处理之前，用抗MFG-E8抗体对NR8383细胞进行预处理，CX3CL1处理的NR8383细胞增强的吞噬活性减弱。我们得出结论，凋亡细胞衍生的CX3CL1(+)微粒通过上调作为桥梁分子的MFG-E8来增强NR8383细胞的吞噬活性，这有助于在凋亡细胞和肺泡巨噬细胞之间形成吞噬突触，以便随后对凋亡细胞进行吞噬清除。
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