Di(2-ethylhexyl)phthalate stimulates Ca2+ entry, chemotaxis and ROS production in human granulocytes

Di(2-ethylhexyl)phthalate (DEHP), a plasticizer widely used in polyvinyl chloride-based medical devices, is known to interfere with immune functions but the underlying molecular mechanisms remain elusive. In this in vitro study, we investigated DEHP effect on intracellular calcium concentration ([Ca2+]i), chemotaxis and reactive oxygen species (ROS) production in human granulocytes. DEHP increased [Ca2+]i by inducing a Ca2+ influx from the extracellular medium. The effect was slow and inhibitable both by the membrane cation channel blockers SKF96365, econazole and 2-aminoethoxy diphenylborate and by the protein kinase C activator phorbol myristate acetate. The plasticizer stimulated both cell chemotaxis and ROS production; however, only the latter effect was dependent on DEHP-induced Ca2+ influx. Collectively, our results indicate that DEHP interaction with human granulocytes leads to multiple and independent effects, each potentially contributing to inappropriate cell activation.