Ban M, Hettich D
Institut National de Recherche et de Sécurité, Avenue de Bourgogne, B.P. no 27, 54501, Cedex, Vandoeuvre, France.
Toxicol Lett. 2001 Jan 3;118(3):129-37. doi: 10.1016/s0378-4274(00)00280-0.
Although increased total serum IgE levels have been suggested as being predictive parameters of airway hypersensitivity caused by low molecular weight chemicals, it is not yet clear what level of serum total IgE in chemically-treated animals would translate to potential risk of inducing an immediate type hypersensitivity in human beings. Quantitative determination of IgE-bearing positive cells induced by chemicals in the tissue, particularly in respiratory airway, could help to resolve this problem. In BALB/c mice, serum total IgE concentrations and tissue IgE-bearing positive cell numbers were investigated following topical exposure to the chemicals, trimellitic anhydride (TMA) and dinitrochlorobenzene (DNCB), known in human as a respiratory and dermal sensitizer, respectively. In groups of mice 8 and 10 weeks of age, there were less individual variations in 25% TMA-induced serum total IgE increase than in other groups of mice 6, 12 and 16 weeks of age. When chemical concentrations of 1, 2 and 3% DNCB and of 6.25, 12.5 and 25% TMA were studied, we observed that the increase in IgE was dose-dependent for both chemicals, r=0.96; P=0.03 for DNCB and r=0.99; P=0.002 for TMA. However, the increase in serum total IgE induced by TMA was at least twice that induced by DNCB and was associated with the numbers of IgE bearing cells in the tracheal lamina propria (r=0.67, P=0.0003). A respiratory hypersensitivity caused by TMA, but not by DNCB, may be partly due to the presence of immuno effector cells bearing IgE at their surface in airway microenvironments, and their presence might be related to the higher level of serum total IgE. The IgE bearing positive cells could, therefore, help to identify chemicals which have the potential risk of inducing an immediate type hypersensitivity in humans.
尽管血清总IgE水平升高被认为是低分子量化学物质引起气道超敏反应的预测参数,但尚不清楚化学处理动物的血清总IgE水平达到何种程度会转化为人类诱发速发型超敏反应的潜在风险。定量测定化学物质在组织中,特别是在呼吸道中诱导产生的IgE阳性细胞,可能有助于解决这一问题。在BALB/c小鼠中,分别局部暴露于均苯四甲酸酐(TMA)和二硝基氯苯(DNCB)这两种化学物质后,研究了血清总IgE浓度和组织中IgE阳性细胞数量。已知这两种物质在人类中分别为呼吸道和皮肤致敏剂。在8周龄和10周龄的小鼠组中,25% TMA诱导的血清总IgE增加的个体差异小于6周龄、12周龄和16周龄的其他小鼠组。当研究1%、2%和3% DNCB以及6.25%、12.5%和25% TMA的化学浓度时,我们观察到两种化学物质的IgE增加均呈剂量依赖性,DNCB的r = 0.96;P = 0.03,TMA的r = 0.99;P = 0.002。然而,TMA诱导的血清总IgE增加至少是DNCB诱导增加的两倍,并且与气管固有层中IgE阳性细胞数量相关(r = 0.67,P = 0.0003)。TMA引起的呼吸道超敏反应,而非DNCB引起的,可能部分归因于气道微环境中表面带有IgE的免疫效应细胞的存在,它们的存在可能与血清总IgE水平较高有关。因此,IgE阳性细胞可能有助于识别具有诱发人类速发型超敏反应潜在风险的化学物质。