TRPM2 Channel-Mediated ROS-Sensitive Ca(2+) Signaling Mechanisms in Immune Cells

Transient receptor potential melastatin 2 (TRPM2) proteins form Ca(2+)-permeable cationic channels that are potently activated by reactive oxygen species (ROS). ROS are produced during immune responses as signaling molecules as well as anti-microbial agents. ROS-sensitive TRPM2 channels are widely expressed in cells of the immune system and located on the cell surface as a Ca(2+) influx pathway in macrophages, monocytes, neutrophils, lymphocytes, and microglia but preferentially within the lysosomal membranes as a Ca(2+) release mechanism in dendritic cells; ROS activation of the TRPM2 channels, regardless of the subcellular location, results in an increase in the intracellular Ca(2+) concentrations. Recent studies have revealed that TRPM2-mediated ROS-sensitive Ca(2+) signaling mechanisms play a crucial role in a number of processes and functions in immune cells. This mini-review discusses the recent advances in revelation of the various roles the TRPM2 channels have in immune cell functions and the implications in inflammatory diseases.