マクロファージにおけるＴＲＰＶ２チャネルの制御機構

抄録

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]