Effect of dialkyl phthalates on the degranulation and Ca2+ response of RBL-2H3 mast cells.
We examined the effect of three dialkyl phthalates, di-n-butylphthalate (DBP), di-isobutylphthalate (DIBP) and di(2-ethylhexyl)phthalate (DEHP), on antigen-induced degranulation of RBL-2H3 mast cells. Exposure to 50-500 microM DBP, 50-500 microM DIBP, and 500 microM DEHP significantly potentiated antigen-induced beta-hexosaminidase release. Without antigen stimulation, the phthalates did not cause any significant increase in degranulation. Next, we examined the Ca2+ response of RBL-2H3 cells after exposure to these phthalates. The cytosolic calcium ion concentration ([Ca2+]i) of the cells clearly increased when the cells were stimulated with 50-500 microM and 50-500 microM DIBP, and increased slightly when stimulated with 50-500 microM DEHP. Digital imaging fluorescence microscope analysis showed that the addition of DBP evoked Ca2+ oscillation in individual mast cells. Finally, we investigated the relationship between the DBP-sensitive Ca2+ stores and thapsigargin (TG)-sensitive Ca2+ stores. A rise in [Ca2+](i) following challenge with DBP after TG was observed, and thus the DBP-sensitive and TG-sensitive Ca2+ stores in RBL-2H3 cells seem to be different. In conclusion, some dialkyl phthalates increase antigen-induced degranulation in RBL-2H3 cells dependent on the increase of [Ca2+]i.
Nakamura
Ryosuke
R
Division of Biochemistry and Immunochemistry, National Institute of Health Sciences, Kamiyoga 1-18-1, Setagaya-ku, Tokyo 158-8501, Japan.
Teshima
Reiko
R
Sawada
Jun ichi
Ji
D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects*; D015550:Cell Degranulation / Q000187:drug effects*; D003993:Dibutyl Phthalate / Q000031:analogs & derivatives / Q000494:pharmacology*; D004051:Diethylhexyl Phthalate / Q000494:pharmacology*; D015759:Ionomycin / Q000378:metabolism; D008407:Mast Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D013997:Time Factors; D014407:Tumor Cells, Cultured
D003993:Dibutyl Phthalate; D015759:Ionomycin; D004051:Diethylhexyl Phthalate; D002118:Calcium