[Background] Macrophage (Mφ) plays crucial roles in immunity and its dysfunction leads to the chronic inflammatory diseases such as arteriosclerosis. Several Mφ functions are modulated by the activation of ionotropic purinergic P2X7 receptor. Caveolin-1 (Cav-1) enables effective intracellular Ca²⁺ signaling by accumulating ion channels within caveolae domain. In this study, we analyzed the functional coupling between Cav-1 and P2X7 receptor using Cav-1 knockout (Cav-1 KO) mice.
[Methods] In murine bone marrow-derived Mφ (BMDM), the expression of Cav-1 was analyzed by real-time PCR and Western Blotting. Interaction of Cav-1 and P2X7 receptor was analyzed by proximal ligation assay. Ca²⁺ influx, K⁺ efflux and reactive oxygen species (ROS) production were measured with confocal microscopy. Cell death was analyzed by LDH assay.
[Results] The expression of Cav-1 was increased by LPS (lipopolysaccharide)-induced inflammatory stimulation in BMDM. Cav-1 was interacted with P2X7 receptor. Thereafter, ATP-evoked Ca²⁺ influx and K⁺ efflux were increased in Cav-1 KO BMDM. ROS production and cell death evoked by ATP were also enhanced in Cav-1 KO BMDM.
[Conclusion] Cav-1 suppresses the activation of P2X7 receptor and modulates immune responses in Mφ. This study may lead to the development of novel drugs for chronic inflammatory diseases.