Sarlo K, Parris J S, Clark E D, Horn P A, Robinson M K, McCay J A, Peachee V L, Veloso Y L, White K L
The Procter & Gamble Company, Miami Valley Laboratories, P.O. Box 538707, Cincinnati, Ohio 45253, USA.
Toxicol Sci. 2000 Dec;58(2):299-305. doi: 10.1093/toxsci/58.2.299.
The mouse intranasal test (MINT) was developed to assess the immunogenic potential of detergent enzymes. The BDF1 mouse (H-2(b/d)), a cross of C57Bl/6 (H-2(b)) x DBA/2 (H-2(d)) has been used for most of the development work. Preliminary data in the CB6F1(H-2(d/b)), a cross of Balb/c (H-2(d)) x C57Bl/6 showed that this strain was similar to the BDF1 in its response to enzymes. These data also showed that the parental strains responded differently to the enzymes. To understand better the influence the major histocompatibility complex (MHC) background has on immune responses to enzymes, 3 different enzymes were tested in 4 inbred strains (C57Bl/6, DBA/2, Balb/c, and C57Bl/10), 2 hybrid strains (BDF1 and CB6F1), and 2 congenic strains (Balb.B10 and B10.D2). BDF1 mice rank enzymes the same as the guinea pig, which in turn correlates with sensitization in occupationally exposed humans. The ranking is based upon the dose of enzyme needed to give one-half maximal IgG1 antibody response (ED(50)) where Termamyl is more potent than Alcalase, which is equipotent to Savinase. The H-2(d) strains ranked the enzymes the same as the BDF1 but generated ED(50)s for the proteases that were one order of magnitude greater than the BDF1 ED(50)s. The response to Termamyl was the same in the two F1 strains and the H-2(d) strains. The H-2(b) strains did not rank the enzymes the same as BDF1 but the ED(50)s for the proteases were similar to the ED(50)s in the F1 strains. The response to Termamyl in the H-2(b) strains was lower than the response in the F1 and H-2(d) strains. Initial data show that the inbred strains will make enzyme-specific IgE antibody to high doses of enzyme with DBA/2 > Balb/c > C57Bl/6 in terms of the robustness of the response. The IgG1 responses in the congenic strains were similar to the responses in the H-2 matched strains. In addition, the antibody response to enzymes was consistent regardless of the source of BDF1 mice. The responses to these enzymes are clearly MHC linked with a role for Class II I-E molecules indicated. The current data strongly support the use of the F1 hybrid as an appropriate strain for evaluating allergic responses to enzymes.
小鼠鼻内试验（MINT）用于评估洗涤剂酶的免疫原性潜力。BDF1小鼠（H-2(b/d)）是C57Bl/6（H-2(b)）和DBA/2（H-2(d)）的杂交品种，大部分研发工作都使用该品种。CB6F1（H-2(d/b)）是Balb/c（H-2(d)）和C57Bl/6的杂交品种，其初步数据表明，该品系对酶的反应与BDF1相似。这些数据还表明，亲本品系对酶的反应不同。为了更好地理解主要组织相容性复合体（MHC）背景对酶免疫反应的影响，在4个近交系（C57Bl/6、DBA/2、Balb/c和C57Bl/10）、2个杂交系（BDF1和CB6F1）以及2个同源系（Balb.B10和B10.D2）中测试了3种不同的酶。BDF1小鼠对酶的排序与豚鼠相同，而豚鼠的排序又与职业暴露人群的致敏情况相关。该排序基于产生最大IgG1抗体反应一半所需的酶剂量（ED(50)），其中地衣芽孢杆菌蛋白酶比碱性蛋白酶更有效，碱性蛋白酶与嗜热栖热菌蛋白酶等效。H-2(d)品系对酶的排序与BDF1相同，但蛋白酶的ED(50)比BDF1的ED(50)大一个数量级。两个F1品系和H-2(d)品系对嗜热栖热菌蛋白酶的反应相同。H-2(b)品系对酶的排序与BDF1不同，但蛋白酶的ED(50)与F1品系相似。H-2(b)品系对嗜热栖热菌蛋白酶的反应低于F1品系和H-2(d)品系。初始数据表明，近交系会针对高剂量的酶产生酶特异性IgE抗体，就反应强度而言，DBA/2 > Balb/c > C57Bl/6。同源系中的IgG1反应与H-2匹配品系中的反应相似。此外，无论BDF1小鼠的来源如何，对酶的抗体反应都是一致的。对这些酶的反应显然与MHC相关，表明II类I-E分子发挥了作用。当前数据有力地支持使用F1杂交种作为评估酶过敏反应的合适品系。
