Abstract：
Macrophages measure the \"eat-me\" signal immunoglobulin G (IgG) to identify targets for phagocytosis. We tested whether prior encounters with IgG influence macrophage appetite. IgG is recognized by the Fc receptor. To temporally control Fc receptor activation, we engineered an Fc receptor that is activated by the light-induced oligomerization of Cry2, triggering phagocytosis. Using this tool, we demonstrate that subthreshold Fc receptor activation primes mouse bone-marrow-derived macrophages to be more sensitive to IgG in future encounters. Macrophages that have previously experienced subthreshold Fc receptor activation eat more IgG-bound human cancer cells. Increased phagocytosis occurs by two discrete mechanisms-a short- and long-term priming. Long-term priming requires new protein synthesis and Erk activity. Short-term priming does not require new protein synthesis and correlates with an increase in Fc receptor mobility. Our work demonstrates that IgG primes macrophages for increased phagocytosis, suggesting that therapeutic antibodies may become more effective after initial priming doses.
摘要：
巨噬细胞测量“吃我”信号免疫球蛋白G（IgG）以识别吞噬作用的靶标。我们测试了先前与IgG的接触是否会影响巨噬细胞的食欲。IgG被Fc受体识别。为了在时间上控制Fc受体激活，我们设计了一种Fc受体，该受体被光诱导的Cry2寡聚化激活，触发吞噬作用。使用这个工具，我们证明亚阈值Fc受体激活使小鼠骨髓源性巨噬细胞在未来遭遇时对IgG更敏感.先前经历过阈值下Fc受体激活的巨噬细胞吞噬更多的IgG结合的人癌细胞。吞噬作用的增加通过两种独立的机制-短期和长期启动发生。长期启动需要新的蛋白质合成和Erk活性。短期引发不需要新的蛋白质合成,并且与Fc受体迀移率的增加相关。我们的工作表明，IgG启动巨噬细胞增加吞噬作用，这表明治疗性抗体在初始启动剂量后可能会变得更有效。
