ABCA1 Transporter Is Involved in the Secretion of CuZn Superoxide Dismutase (SOD)-1 by Activated Human T Lymphocytes

The pivotal role of reactive oxygen species (ROS), especially peroxides, in multiple cell signalling pathways has been well-established. Superoxide dismutase 1 (SOD-1) represents a major intracellular source of hydrogen peroxide. Antigen-dependent activation of human T lymphocytes has been previously described by us to induce both SOD-1 production and secretion by T cells. SOD-1 mediated pathways have also been described to deliver proinflammatory signals and to affect the differentiation of immune-suppressor subsets (Treg). The mechanisms underlying extracellular SOD-1 export by activated T cells remain largely undefined. Indeed, SOD-1, like the leaderless proteins, is unable to exploit the conventional trans-Golgi vesicular secretion pathway. Here, we propose that ABCA1 transporters play a role in the mechanisms underlying SOD-1 secretion by activated T cells. Indeed, ABC transporter inhibition by using glyburide significantly decreases SOD-1 secretion by antigen-triggered human T cells in vitro. The effect has been confirmed by using four different detection techniques, as represented by Western blotting, ELISA, flow cytometry and confocal microscopy. Collectively, our findings indicate that ABCA1 transporter-dependent secretion supports the vesicular secretory machinery and might contribute to the extracellular release of SOD-1 by activated T cells. This mechanism highlights ABCA1 as a promising molecular target for therapeutic modulation of deranged immune activation.