Abstract
In phagocytes such as neutrophil, macrophage and microglia, regulation of pH of phagosomes and cytoplasm is critical for pathogen killing, antigen presentation and elimination of abnormal cells such as apoptotic cells and cancer cells. NADPH oxidase that mediates ROS generation during phagocytosis, called respiratory burst, leaves proton in the cytoplasm while it releases superoxide anions. This causes charge imbalance in the cytoplasm leading to membrane depolarization and acidification. Proton also needs to be supplied to phagosome for production of hydrogen peroxide and HOCl. Voltage-gated proton channel (Hv channel) has been believed to be the most likely candidate for these roles in phagocytosis. However, its molecular basis has long been elusive. We have reported a protein called VSOP (voltage-sensor only protein, also called as Hv1) that in heterologous expression recapitulates most properties of endogenous Hv currents (Sasaki et al, Science, 2006). To understand roles of VSOP in phagocytosis, immunohistochemistry and western blot analysis were performed with VSOP-specific antibody. Prominent expression was detected in many types of cells in spleen. Induction of VSOP protein expression was also studied in an injured tissue: cryoinjury was induced in adult mouse brain. Up to one month, population of VSOP-positive cells including neutrophils, lymphocytes and monocytes were observed around the injured site. We are also studying detailed pattern of subcellular localization of VSOP proteins in these cells. [J Physiol Sci. 2007;57 Suppl:S50]