Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 3, 701-707
eCollection

Trimellitic Anhydride Induces Low-Grade Mast Cell Degranulation Without Specific IgE

Affiliations

Trimellitic Anhydride Induces Low-Grade Mast Cell Degranulation Without Specific IgE

Kazuhiro Ogi et al. Toxicol Rep.

Abstract

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 Ca2+ 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.

Keywords: BSA, bovine serum albumin; DNP, dinitrophenylated; HMW, high molecular weight; IL, interleukin; IgE, immediate immunoglobulin E; IgE, immunoglobulin E; LMW, low molecular weight; Mast cell; OA, occupational asthma; OR, occupational rhinitis; Occupational rhinitis; PD, piecemeal degranulation; Respiratory hypersensitivity; TMA, trimellitic anhydride; Trimellitic anhydride.

Figures

Fig. 1
Fig. 1
Analysis of mast cell degranulation induced by low-molecular-weight substances. Results are the mean values ± SD from 3 independent experiments.
Fig. 2
Fig. 2
Immunobloting analysis of the effect of trimellitic anhydride (TMA) on mast cells. The phosphorylation of whole cellular molecules by antigen or TMA. Results are representative of 3 independent experiments.
Fig. 3
Fig. 3
Suppression of RBL-2H3 cell degranulation in the presence or absence of Ca2+. Degranulation by antigen or calcium ionophore in the presence or absence of Ca2+. These experiments were conducted in the absence of anti-DNP IgE. Results are the mean values ± SD from 3 independent experiments.
Fig. 4
Fig. 4
Degranulation of mast cells by trimellitic anhydride in the presence or absence of Ca2+. Results are the mean values ± SD from 3 independent experiments.
Fig. 5
Fig. 5
Immunobloting analysis of the effect of trimellitic anhydride (TMA) on mast cells. The phosphorylation of ERK mediated by antigen or TMA. Results are representative of 3 independent experiments.
Fig. 6
Fig. 6
Trypan blue exclusion assay. The percentage of dead cells among total cell number are shown after vehicle or 10 mM TMA exposure for 1 h. Results are the mean values ± SD from 3 independent experiments.

Similar articles

See all similar articles

References

    1. Braniuk J.N., Kaliner M.A. Functional activity of upper-airway nerves. In: Busse W., Holgate S., editors. Sasthma and Rhinitis. Blackwell Scientific; Cambridge, MA: 1995. pp. 652–667.
    1. Castano R., Theriault G. Defining and classifying occupational rhinitis. J. Laryngol. Otol. 2006;120:812–817. - PubMed
    1. Sirakusa A., Desrosiers M., Marabini A. Epidemiology of occupational rhinitis:prevelence, aetiology and determinants. Clin. Exp. Allergy. 2000;30:1519–1534. - PubMed
    1. Haenuki Y., Matsushita K., Futatsugi-Yumikura S., Ishii K.J., Kawagoe T., Imoto Y., Fujieda S., Yasuda M., Hisa Y., Akira S., Nakanishi K., Yoshimoto T. A critical role of IL-33 in experimental allergic rhinitis. J. Allergy Clin. Immunol. 2012;130:184–194. - PubMed
    1. Ortega E., Schweitzer-Stenner R., Pecht I. Possible orientational constraints determine secretory signals induced by aggregation of IgE receptors on mast cells. EMBO J. 1988;7:4101–4109. - PMC - PubMed

LinkOut - more resources

Feedback