Trimellitic anhydride induces low-grade mast cell degranulation without specific IgE

OBJECTIVES: Low-molecular-weight (LMW) substances are known to be causative agents of occupational asthma (OA) and occupational rhinitis (OR). Although most LMW substances are irritants or allergens, some can cause immediate type immunoglobulin E (IgE)-mediated allergic reactions. Trimellitic anhydride (TMA) is one such LMW substance, which is known as an immunological sensitizer. However, the exact molecular biological details of the effects of TMA remain unclear. METHODS: We measured the β-hexosaminidase release from mast cells after directly exposing the cells to various LMW substances. The tyrosine phosphorylation of whole cellular molecules and the phosphorylation of extracellular signal-regulated kinase (ERK) were assessed by immunoblot assay. RESULTS: Among the LMW substances tested, only TMA induced β-hexosaminidase release. However, the mast cell degranulation induced by TMA was lower than that induced by an antigen or a calcium ionophore. Moreover, the pattern of tyrosine phosphorylation of whole cellular molecules was quite different between IgE-mediated antigen stimulation and TMA exposure. The TMA effect on mast cells was independent of not only IgE but also Ca(2+) influx. ERK phosphorylation was not detected in mast cells exposed to TMA. CONCLUSIONS: TMA induced mild degranulation of mast cells without IgE, even though the phosphorylation of ERK was not detected. This reaction suggests that TMA affects humans even upon first exposure. Therefore, it is imperative to avoid human exposure to high concentrations of TMA. In order to stop the development of severe asthma in individuals with OR, we need to be able to identify cases of OR caused by TMA as soon as possible.