Hillebrand J A, Thorne P S, Karol M H
Toxicol Appl Pharmacol. 1987 Jul;89(3):449-56. doi: 10.1016/0041-008x(87)90164-5.
We have previously reported the development of pulmonary sensitivity in guinea pigs exposed for 5 consecutive days to bacterial subtilisin in concentrations ranging from 1.9 to 15.0 mg proteolytic enzyme/m3. Animals exposed to lesser concentrations of 0.0083 and 0.041 mg/m3 failed to demonstrate this sensitivity. In the same study, animals exposed for 11 weeks to a subtilisin concentration of 0.00068 mg/m3 followed by 6 weeks to 0.0051 mg/m3 failed to demonstrate pulmonary sensitivity. We report here the antibody response in these animals. Both an enzyme-linked immunosorbent assay and a latex agglutination assay were developed for antibody detection. A concentration-related antibody response was detected in animals which had received acute subtilisin exposures of 0.0083 to 1.9 mg/m3. Antibody titers were not increased further upon exposure to higher subtilisin concentrations. A single 3-hr exposure to 1.9 mg/m3 resulted in the same antibody response as that produced following 5 days of exposure to the same concentration. The cumulative 17-week exposure of 1.12 mg/m3 X hr subtilisin resulted in 36% (9 of 25) of the animals producing significant levels of IgG or IgM antibodies. None of these animals demonstrated pulmonary sensitivity. These results indicate that the circulating antibody titer reflected antigen exposure levels and occurred at exposures below those necessary for production of pulmonary sensitivity.
我们之前曾报道，豚鼠连续5天暴露于浓度范围为1.9至15.0 mg蛋白水解酶/m³的枯草杆菌蛋白酶中会出现肺部敏感性。暴露于浓度较低的0.0083和0.041 mg/m³的动物未表现出这种敏感性。在同一研究中，暴露于浓度为0.00068 mg/m³的枯草杆菌蛋白酶11周，随后暴露于0.0051 mg/m³ 6周的动物也未表现出肺部敏感性。我们在此报告这些动物的抗体反应。开发了酶联免疫吸附测定法和乳胶凝集测定法用于抗体检测。在接受0.0083至1.9 mg/m³急性枯草杆菌蛋白酶暴露的动物中检测到浓度相关的抗体反应。暴露于更高的枯草杆菌蛋白酶浓度时，抗体滴度没有进一步升高。单次3小时暴露于1.9 mg/m³产生的抗体反应与暴露于相同浓度5天产生的反应相同。累积17周暴露于1.12 mg/m³·小时的枯草杆菌蛋白酶导致25只动物中有36%（9只）产生显著水平的IgG或IgM抗体。这些动物均未表现出肺部敏感性。这些结果表明，循环抗体滴度反映了抗原暴露水平，且在低于产生肺部敏感性所需的暴露水平时就会出现。
