Inhibition of IgE-induced mast cell activation by ethyl tertiary-butyl ether, a bioethanol-derived fuel oxygenate.
OBJECTIVE
The effect of ethyl tertiary-butyl ether (ETBE), which is widely used as a fuel oxygenate commonly produced from bioethanol, on immunoglobulin (Ig)E-dependent mast cell activation was investigated.


METHODS
The rat mast cell line RBL2H3 sensitised with monoclonal anti-ovalbumin IgE was challenged with ovalbumin in the presence or absence of ETBE, tert-butanol (TBA), which is the main metabolite of ETBE in humans, and ethanol. Degranulation of RBL2H3 was examined by the release of beta-hexosaminidase. To understand the mechanisms responsible for regulating mast cell function, the effects of ETBE, TBA and ethanol on the levels of intracellular calcium, phosphorylation of Akt (as a marker of phosphatidylinositol 3-kinase) and global tyrosine phosphorylation were also measured as indicators of mast cell activation.


RESULTS
In the presence of ETBE, TBA or ethanol, IgE-induced release of beta-hexosaminidase was decreased. These compounds also attenuated the IgE-mediated increase in the levels of intracellular Ca(2+), phosphorylation of Akt and global tyrosine phosphorylation in RBL2H3 cells.


CONCLUSIONS
ETBE, TBA and ethanol inhibited mast cell degranulation by inhibiting the increase in intracellular calcium ion concentration and activation of phosphatidylinositol 3-kinase and protein tyrosine kinase activation, suggesting that exposure to ETBE might affect immune responses, particularly in allergic diseases.
Yamaki
Kouya
K
Department of Pharmacology, Kobe Pharmaceutical University, Hyogo 658-8558, Japan. yam@kobepharma-u.ac.jp
Yoshino
Shin
S
D000818:Animals; D002118:Calcium / Q000378:metabolism; D015550:Cell Degranulation / Q000187:drug effects*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D000431:Ethanol / Q000494:pharmacology; D005019:Ethyl Ethers / Q000633:toxicity*; D005579:Fossil Fuels; D007073:Immunoglobulin E / Q000494:pharmacology*; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D010047:Ovalbumin / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D014443:Tyrosine / Q000378:metabolism; D020002:tert-Butyl Alcohol / Q000494:pharmacology
D005019:Ethyl Ethers; D005579:Fossil Fuels; D007073:Immunoglobulin E; D000431:Ethanol; C098546:ethyl tert-butyl ether; D014443:Tyrosine; D010047:Ovalbumin; D051057:Proto-Oncogene Proteins c-akt; D020002:tert-Butyl Alcohol; D002118:Calcium