Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland.
Department of Cellular Physiology and Metabolism, University of Geneva, Geneva, Switzerland.
Adv Exp Med Biol. 2020;1246:103-128. doi: 10.1007/978-3-030-40406-2_7.
Calcium (Ca) is a ubiquitous second messenger involved in the regulation of numerous cellular functions including vesicular trafficking, cytoskeletal rearrangements and gene transcription. Both global as well as localized Ca signals occur during phagocytosis, although their functional impact on the phagocytic process has been debated. After nearly 40 years of research, a consensus may now be reached that although not strictly required, Ca signals render phagocytic ingestion and phagosome maturation more efficient, and their manipulation make an attractive avenue for therapeutic interventions. In the last decade many efforts have been made to identify the channels and regulators involved in generating and shaping phagocytic Ca signals. While molecules involved in store-operated calcium entry (SOCE) of the STIM and ORAI family have taken center stage, members of the canonical, melastatin, mucolipin and vanilloid transient receptor potential (TRP), as well as purinergic P2X receptor families are now recognized to play significant roles. In this chapter, we review the recent literature on research that has linked specific Ca-permeable channels and regulators to phagocytic function. We highlight the fact that lipid mediators are emerging as important regulators of channel gating and that phagosomal ionic homeostasis and Ca release also play essential parts. We predict that improved methodologies for measuring these factors will be critical for future advances in dissecting the intricate biology of this fascinating immune process.
钙（Ca）是一种普遍存在的第二信使，参与调节许多细胞功能，包括囊泡运输、细胞骨架重排和基因转录。吞噬作用过程中会发生全局和局部 Ca 信号，尽管它们对吞噬作用过程的功能影响一直存在争议。经过近 40 年的研究，现在可能达成共识，尽管 Ca 信号不是严格必需的，但它们使吞噬作用的摄取和吞噬体成熟更有效，对其进行操作为治疗干预提供了有吸引力的途径。在过去十年中，人们做出了许多努力来识别参与产生和塑造吞噬 Ca 信号的通道和调节剂。虽然涉及储存操纵钙进入（SOCE）的 STIM 和 ORAI 家族的分子占据了中心位置，但现在已经认识到经典、melastatin、mucolipin 和 vanilloid 瞬时受体电位（TRP）以及嘌呤能 P2X 受体家族的成员也发挥着重要作用。在本章中，我们回顾了最近关于将特定的 Ca 渗透性通道和调节剂与吞噬功能联系起来的研究文献。我们强调了这样一个事实，即脂质介质正在成为通道门控的重要调节剂，并且吞噬体离子稳态和 Ca 释放也起着至关重要的作用。我们预测，用于测量这些因素的改进方法对于未来在剖析这个迷人的免疫过程的复杂生物学方面的进展至关重要。
