3-Chloro-l,2-propanediol (3-MCPD), a Carcinogenic Food Contaminant, Inhibits Mast Cell Activation via Affecting Ca~(2+) Mobilization

摘要

Recently, there has been growing concern over the health risks of exposure to 3-chloro-1,2-propanediols (3-MCPD), a food contaminant. In the present study, we clarified the effects of 3-MCPD on mast cell activation. The rat mast cell line RBL2H3 sensitized with monoclonal anti-ovalbumin (OVA) IgE was challenged with OVA or activated by ionomycin in the presence or absence of 3-MCPD. Degranulation of RBL2H3 cells was examined by the p-hexosaminidase release. To understand the mechanisms responsible for regulating mast cell functions, the effects of 3-MCPD on the levels of intracellular Ca~(2+) were also measured. IgE/antigen- and ionomycin-induced p-hexosaminidase release was significantly attenuated by 3-MCPD at 0.3 to 2.4 %. Consistent with its inhibitory effect on (3-hexosaminidase release, 3-MCPD attenuated the increases of intracellular Ca~(2+) concentration induced by IgE/OVA or ionomycin. 3-MCPD obviously decreased the transient increase of intracellular Ca~(2+) in Ca~(2+)-free medium induced by IgE/antigen but not by ionomycin, suggesting that 3-MCPD blunts the signaling cascade from FcsRI to Ca~(2+) release from endoplasmic reticulum. Moreover, the increase of intracellular Ca~(2+) concentration by an addition of extracellular Ca~(2+) after thapsigargin/EGTA-pretreatment, namely store-operated calcium entry (SOCE), was inhibited by 3-MCPD. These findings indicate that 3-MCPD inhibited intracellular Ca~(2+) increase via both the inhibition of Ca~(2+) release from intracellular Ca~(2+) stores and SOCE, thus decreasing IgE/antigen- and ionomycin-induced mast cell degranulation. High exposure to 3-MCPD might affect immune responses, especially in allergic disorders.