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 ([Ca(2+)](i)), chemotaxis and reactive oxygen species (ROS) production in human granulocytes. DEHP increased [Ca(2+)](i) by inducing a Ca(2+) 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 Ca(2+) influx. Collectively, our results indicate that DEHP interaction with human granulocytes leads to multiple and independent effects, each potentially contributing to inappropriate cell activation.
DI(2-ETHYLHEXYL)PHTHALATE STIMULATES Ca2+ ENTRY, CHEMOTAXIS AND ROS PRODUCTION IN HUMAN GRANULOCYTES / Palleschi, S; Rossi, B; Diana, L.; Silvestroni, Leopoldo. - In: TOXICOLOGY LETTERS. - ISSN 0378-4274. - STAMPA. - 187:(2009), pp. 52-57. [10.1016/j.toxlet.2009.01.031]
DI(2-ETHYLHEXYL)PHTHALATE STIMULATES Ca2+ ENTRY, CHEMOTAXIS AND ROS PRODUCTION IN HUMAN GRANULOCYTES
SILVESTRONI, Leopoldo
2009
Abstract
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 ([Ca(2+)](i)), chemotaxis and reactive oxygen species (ROS) production in human granulocytes. DEHP increased [Ca(2+)](i) by inducing a Ca(2+) 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 Ca(2+) influx. Collectively, our results indicate that DEHP interaction with human granulocytes leads to multiple and independent effects, each potentially contributing to inappropriate cell activation.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
