Blaikie L, Basketter D A
Unilever Safety and Environmental Assurance Centre, Sharnbrook, Bedford, UK.
Food Chem Toxicol. 1999 Aug;37(8):897-904. doi: 10.1016/s0278-6915(99)00069-1.
Proteins, including enzymes, have the potential to behave as respiratory allergens. In consequence, guinea pig methods have been developed which permit an assessment to be made of their respiratory allergenic/antigenic potential relative to an appropriate reference substance. Recently, a murine model, the mouse intranasal test (MINT) has been proposed as a potential alternative. However, to be of value, the new method should give a rank order of relative potency for a range of proteins which correlates with that found in guinea pig models and in human experience. Using the mouse strain recommended for the MINT, BDF1, in an extensive intralaboratory assessment, the relative potency of several of the eight proteins used was at variance with that expected from the historic data. Where genetic factors are important, as in the assessment of antigenicity, the rank order for a range of proteins in a particular inbred or F1 hybrid strain may not reflect that in humans. To examine whether the earlier observations were a strain rather than a species dependent phenomenon, five proteins of varying antigenic potency previously tested using the BDF1 strain were selected and tested using the MINT protocol in BALB/c, CBA/Ca and CB6F1 inbred/F1 hybrid strains, as well as in the outbred Swiss S strain. The results clearly indicated that the relative potency of the proteins was dependent on the mouse strain used and thus with haplotype. When assessed against the standard reference enzyme, Alcalase (a process used for the establishment of occupational exposure guidelines), the rank order was strain dependent and results from none of the mouse strains would have led to similar conclusions to those derived from existing models and the human epidemiological data. Based on the presently available information, it is not possible to be certain that any mouse model reliant on the responsiveness of a particular strain (including the MINT) might not lead to an incorrect estimation of respiratory antigenic and thus allergenic potency. In consequence, the MINT may not be viable as a model for the assessment of the relative ability of proteins to behave as respiratory allergens.
包括酶在内的蛋白质有可能表现为呼吸道变应原。因此，已经开发出豚鼠实验方法，能够评估其相对于合适参考物质的呼吸道变应原/抗原潜力。最近，有人提出一种小鼠模型，即小鼠鼻内试验（MINT）作为一种潜在的替代方法。然而，要具有价值，新方法应该给出一系列蛋白质的相对效力排名顺序，该顺序要与豚鼠模型和人类经验中的结果相关。在一项广泛的实验室内评估中，使用推荐用于MINT的BDF1小鼠品系，所使用的8种蛋白质中有几种的相对效力与历史数据预期的不同。在评估抗原性等遗传因素起重要作用的情况下，特定近交系或F1杂交品系中一系列蛋白质的排名顺序可能无法反映人类的情况。为了研究早期观察结果是品系依赖性而非物种依赖性现象，选择了之前使用BDF1品系测试过的5种抗原效力不同的蛋白质，并使用MINT方案在BALB/c、CBA/Ca和CB6F1近交系/F1杂交品系以及远交瑞士S品系中进行测试。结果清楚地表明，蛋白质的相对效力取决于所使用的小鼠品系，因此也取决于单倍型。当与标准参考酶碱性蛋白酶（一种用于确定职业接触指南的方法）进行比较评估时，排名顺序取决于品系，没有一个小鼠品系的结果会得出与现有模型和人类流行病学数据类似的结论。根据目前可得的信息，无法确定任何依赖特定品系反应性的小鼠模型（包括MINT）是否可能导致对呼吸道抗原性以及因此变应原效力的错误估计。因此，MINT作为评估蛋白质作为呼吸道变应原相对能力的模型可能不可行。
