PMID- 28959595 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20200930 IS - 2214-7500 (Print) IS - 2214-7500 (Electronic) IS - 2214-7500 (Linking) VI - 3 DP - 2016 TI - Trimellitic anhydride induces low-grade mast cell degranulation without specific IgE. PG - 701-707 LID - 10.1016/j.toxrep.2016.09.001 [doi] AB - 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 beta-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 beta-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. FAU - Ogi, Kazuhiro AU - Ogi K AD - Division of Otorhinolaryngology Head and Neck Surgery, Department of Sensory and Locomotor Medicine, Faculty of Medical Sciences, University of Fukui, Fukui 910-1193, Japan. FAU - Takabayashi, Tetsuji AU - Takabayashi T AD - Division of Otorhinolaryngology Head and Neck Surgery, Department of Sensory and Locomotor Medicine, Faculty of Medical Sciences, University of Fukui, Fukui 910-1193, Japan. FAU - Yamada, Takechiyo AU - Yamada T AD - Division of Otorhinolaryngology Head and Neck Surgery, Department of Sensory and Locomotor Medicine, Faculty of Medical Sciences, University of Fukui, Fukui 910-1193, Japan. FAU - Sakashita, Masafumi AU - Sakashita M AD - Division of Otorhinolaryngology Head and Neck Surgery, Department of Sensory and Locomotor Medicine, Faculty of Medical Sciences, University of Fukui, Fukui 910-1193, Japan. FAU - Kanno, Masafumi AU - Kanno M AD - Division of Otorhinolaryngology Head and Neck Surgery, Department of Sensory and Locomotor Medicine, Faculty of Medical Sciences, University of Fukui, Fukui 910-1193, Japan. FAU - Narita, Norihiko AU - Narita N AD - Division of Otorhinolaryngology Head and Neck Surgery, Department of Sensory and Locomotor Medicine, Faculty of Medical Sciences, University of Fukui, Fukui 910-1193, Japan. FAU - Fujieda, Shigeharu AU - Fujieda S AD - Division of Otorhinolaryngology Head and Neck Surgery, Department of Sensory and Locomotor Medicine, Faculty of Medical Sciences, University of Fukui, Fukui 910-1193, Japan. LA - eng PT - Journal Article DEP - 20160907 PL - Ireland TA - Toxicol Rep JT - Toxicology reports JID - 101630272 PMC - PMC5616080 OTO - NOTNLM OT - BSA, bovine serum albumin OT - DNP, dinitrophenylated OT - HMW, high molecular weight OT - IL, interleukin OT - IgE, immediate immunoglobulin E OT - IgE, immunoglobulin E OT - LMW, low molecular weight OT - Mast cell OT - OA, occupational asthma OT - OR, occupational rhinitis OT - Occupational rhinitis OT - PD, piecemeal degranulation OT - Respiratory hypersensitivity OT - TMA, trimellitic anhydride OT - Trimellitic anhydride EDAT- 2017/09/30 06:00 MHDA- 2017/09/30 06:01 PMCR- 2016/09/07 CRDT- 2017/09/30 06:00 PHST- 2016/03/14 00:00 [received] PHST- 2016/09/01 00:00 [revised] PHST- 2016/09/02 00:00 [accepted] PHST- 2017/09/30 06:00 [entrez] PHST- 2017/09/30 06:00 [pubmed] PHST- 2017/09/30 06:01 [medline] PHST- 2016/09/07 00:00 [pmc-release] AID - S2214-7500(16)30068-3 [pii] AID - 10.1016/j.toxrep.2016.09.001 [doi] PST - epublish SO - Toxicol Rep. 2016 Sep 7;3:701-707. doi: 10.1016/j.toxrep.2016.09.001. eCollection 2016.