マクロファージにおけるＴＲＰＶ２チャネルの制御機構

The TRPV2 channel is expressed in various tissues including neurons, neuroendocrine cells and blood cells including macrophages. We examined the regulation of the TRPV2 channel in macrophages. In serum-free condition, immunoreactivity of TRPV2 was detected largely in cytoplasm. Addition of a chemotactic peptide fMLP induced translocation of the TRPV2 to the plasma membrane. In accordance with this, fMLP increased the Cs⁺ current, which was inhibited by ruthenium red and the transfection of the dominant-negative mutant of TRPV2. fMLP-induced translocation of the TRPV2 was blocked by PI 3-kinase inhibitors and pretreatment with pertussis toxin. When cytoplasmic calcium concentration ([Ca²⁺]_c) was monitored by using fura-2, fMLP induced a rapid and sustained elevation of [Ca²⁺]_c, the latter of which was abolished by removal of extracellular calcium. Addition of ruthenium red or transfection of the dominant-negative mutant of TRPV2 did not affect the initial rise but blocked the sustained phase of fMLP-induced [Ca²⁺]_c response. In stimulated macrophages, TRPV2 localized in the podosome, a microdomain involved in adhesion and migration, and colocalized with Rho family small G proteins. Transfection of the dominant-negative Rac inhibited translocation of TRPV2. Finally, addition of ruthenium red or transfection of dominant-negative mutant of TRPV2 inhibited chemotaxis of macrophage induced by fMLP. These results indicate that fMLP induces translocation of TRPV2 by a PI 3-kinase dependent mechanism and this translocation is important for sustained elevation of [Ca²⁺]_c in macrophage. [J Physiol Sci. 2006;56 Suppl:S11]