Di(2-ethylhexyl)phthalate stimulates Ca(2+) 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 ([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.
Dept. of Hematology, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy. simonetta.palleschi@iss.it
Simonetta
S
Palleschi
Barbara
B
Rossi
Loretta
L
Diana
Leopoldo
L
Silvestroni
D000328:Adult; D001896:Boron Compounds / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects; D002633:Chemotaxis / Q000187:drug effects*; D004051:Diethylhexyl Phthalate / Q000633:toxicity*; D004336:Drug Antagonism; D004464:Econazole / Q000494:pharmacology; D006098:Granulocytes / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D010968:Plasticizers / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D001896:Boron Compounds; D002121:Calcium Channel Blockers; D007093:Imidazoles; D010968:Plasticizers; D017382:Reactive Oxygen Species; D004464:Econazole; D004051:Diethylhexyl Phthalate; C109986:2-aminoethoxydiphenyl borate; C063159:1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium