Zhang Xing-Dong, Andrew Michael E, Hubbs Ann F, Siegel Paul D
Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia 26505, USA.
Toxicol Sci. 2006 Dec;94(2):322-9. doi: 10.1093/toxsci/kfl107. Epub 2006 Sep 18.
Trimellitic anhydride (TMA) is a cause of asthma in man. Dose-dependent TMA-specific IgE, histopathology, and airway responses after sensitization by inhalation were examined in the Brown Norway rat. Rats were exposed to 0.04, 0.4, 4, or 40 mg/m3 TMA aerosol for 10 min, once a week, over 10 weeks. All lower exposures were, subsequently, rechallenged to 40 mg/m3 TMA aerosol. All rats received a sham exposure 1 week prior to the first TMA exposure. Following the sham exposure and weekly after each TMA exposure, TMA-specific IgE and both early-phase airway response (EAR) and late-phase airway response (LAR) were measured using enhanced pause (Penh). All rats sensitized by 40 mg/m3 TMA developed specific IgE, EAR, and LAR to one or more of the challenges to 40 mg/m3 TMA. TMA of 4 mg/m3 induced a much lower, but stable, specific IgE response. EAR and LAR were observed only after a 40 mg/m3 TMA rechallenge in this group, but it was much larger than that observed in the 40 mg/m3 TMA-sensitized and challenged group. Exposure-dependent histopathological changes noted included eosinophilic granulomatous interstitial pneumonia, perivascular eosinophil infiltrates, bronchial-associated lymphoid tissue hyperplasia, and peribronchiolar plasma cell infiltrates.
偏苯三酸酐（TMA）是人类哮喘的一个病因。在棕色挪威大鼠中，研究了吸入致敏后剂量依赖性的TMA特异性IgE、组织病理学和气道反应。大鼠每周一次，每次暴露于0.04、0.4、4或40 mg/m³的TMA气雾剂中10分钟，持续10周。随后，所有较低剂量暴露组的大鼠都再次暴露于40 mg/m³的TMA气雾剂中。所有大鼠在首次TMA暴露前1周接受假暴露。在假暴露后以及每次TMA暴露后的每周，使用增强间歇（Penh）测量TMA特异性IgE以及早期气道反应（EAR）和晚期气道反应（LAR）。所有经40 mg/m³ TMA致敏的大鼠对40 mg/m³ TMA的一次或多次激发产生了特异性IgE、EAR和LAR。4 mg/m³的TMA诱导了低得多但稳定的特异性IgE反应。在该组中，仅在40 mg/m³ TMA再次激发后观察到EAR和LAR，但比在40 mg/m³ TMA致敏和激发组中观察到的要大得多。观察到的与暴露相关的组织病理学变化包括嗜酸性肉芽肿性间质性肺炎、血管周围嗜酸性粒细胞浸润、支气管相关淋巴组织增生和细支气管周围浆细胞浸润。
