Science Topics – 102

The voltage-gated proton channel Hv1/VSOP inhibits neutrophil granule release
Yoshifumi Okochi (Yasushi Okamura)

Voltage-gated proton channel has been known to help the activity of NADPH oxidase, an enzyme generating reactive oxygen species (ROS), in phagocytes. In 2006, our laboratory discovered this molecule named Hv1/VSOP. The functions of this channel are analyzed worldwide in molecular, cellular and animal level and new insights are reported one after another. In this study, we found that the proton channel inhibits exocytosis of azurophilic granules in neutrophils. Neutrophils act in first line of defense and eliminate invaded pathogens by producing ROS and secreting degradative enzymes. Large amount of secretion of these enzymes in neutrophils is known to cause excess inflammation, leading to some kinds of diseases. When Hv/VSOP-deficient neutrophils were stimulated, these cells released more granules than wild-type cells, leading to increased activities of myeloperoxidase, an enzyme producing hypochlorous acid (HOCl), and degradative enzyme “elastase”. This enhanced granule release was caused by at least the involvement of membrane potential at plasma membrane. In animal level, Hv1/VSOP-deficient mice exhibited inflammation in lung severer than wild-type mice upon Candida infection. These results suggest that Hv1/VSOP protects excess inflammation in defense against infection through the inhibition of excess release of granules in neutrophils.

Okochi Y*, Aratani Y, Adissu HA, Miyawaki N, Sasaki M, Suzuki K, Okamura Y*. The voltage-gated proton channel Hv1/VSOP inhibits neutrophil granule release. J Leukoc Biol. 2016 Jan;99(1):7-19. doi: 10.1189/jlb.3HI0814-393R. *Corresponding authors

Integrative Physiology, Graduate School of Medicine, Osaka University