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.
Palleschi
Simonetta
S
Dept. of Hematology, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy. simonetta.palleschi@iss.it
Rossi
Barbara
B
Diana
Loretta
L
Silvestroni
Leopoldo
L
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