Arakawa H, Lötvall J, Kawikova I, Tee R, Hayes J, Löfdahl C G, Taylor A J, Skoogh B E
Division of Clinical Pharmacology (Department of Pharmacology), Göteborg University, Sweden.
J Allergy Clin Immunol. 1993 Sep;92(3):425-34. doi: 10.1016/0091-6749(93)90121-u.
Trimellitic anhydride (TMA) is a low molecular weight chemical that may cause occupational asthma in human beings. The objectives of this study were to determine the time course of immune and airway responses to TMA in guinea pigs and to relate the immunologic response to the immediate responses in lung resistance (RL) and plasma exudation induced by allergen challenge.
We studied the effects of time course after sensitization on airway response to TMA in guinea pigs actively sensitized to free TMA, given by intradermal injection (0.1 ml of 0.3% TMA in corn oil). During weeks 1, 2, 3, 5, and 8 after sensitization, anesthetized animals were challenged with TMA conjugated to guinea pig serum albumin (TMA-GPSA), instilled via the airway route. Nonsensitized animals were challenged with the same amount of conjugate 4 weeks after intradermal injection of corn oil only. In the same animal, we measured both RL to monitor airflow obstruction and extravasation of Evans blue dye (20 mg/kg) to quantify airway plasma exudation.
Instillation of TMA-GPSA (0.5%; 50 microliters) into the tracheal lumen caused a significant increase in RL, reaching a maximum at 2.5 minutes after the instillation in the 1-week group (9.0 +/- 5.9 cm H2O/ml/sec) and between 5 and 6 minutes in the 2-, 3-, 5-, and 8-week groups (9.4 +/- 4.8, 12.7 +/- 5.5, 3.7 +/- 1.1, and 1.7 +/- 0.2 cm H2O/ml/sec, respectively). The maximal increase in RL after the challenge in nonsensitized animals was 0.39 +/- 0.05 cm H2O/ml/sec. TMA-GPSA also produced significant extravasation of Evans blue dye at all airway levels in the sensitized groups, and the amount of dye in the peripheral airways was significantly greater than that in the trachea. Furthermore, the level of Evans blue dye in airway tissue increased with the time after sensitization, up to the latest time point tested (8 weeks). Specific IgG1 antibodies to TMA-GPSA demonstrated by ELISA were detected in all animals in the 3-, 5-, and 8-week groups, with maximal levels 5 weeks after sensitization. Specific IgG1 titers to TMA-GPSA significantly correlated with the level of Evans blue dye induced by challenge with TMA-GPSA but not with the increase in RL.
Intradermal sensitization to free TMA induces specific airway allergy for a long period after sensitization. Specific IgG1 antibodies to allergen may influence allergen-induced plasma exudation rather than the airflow obstruction in this animal model of TMA-induced asthma.
偏苯三酸酐（TMA）是一种低分子量化学物质，可能导致人类职业性哮喘。本研究的目的是确定豚鼠对TMA的免疫和气道反应的时间进程，并将免疫反应与变应原激发诱导的肺阻力（RL）即时反应和血浆渗出相关联。
我们研究了致敏后时间进程对主动致敏于游离TMA的豚鼠气道对TMA反应的影响，通过皮内注射（0.1 ml含0.3% TMA的玉米油）给予。在致敏后的第1、2、3、5和8周，对麻醉动物经气道途径滴注与豚鼠血清白蛋白偶联的TMA（TMA-GPSA）进行激发。仅皮内注射玉米油4周后，对未致敏动物用相同量的偶联物进行激发。在同一动物中，我们测量RL以监测气流阻塞，并测量伊文思蓝染料（20 mg/kg）的外渗以量化气道血浆渗出。
向气管腔内滴注TMA-GPSA（0.5%；50微升）导致RL显著增加，在1周组滴注后2.5分钟达到最大值（9.0±5.9 cm H2O/ml/秒），在2、3、5和8周组中在5至6分钟达到最大值（分别为9.4±4.8、12.7±5.5、3.7±1.1和1.7±0.2 cm H2O/ml/秒）。未致敏动物激发后RL的最大增加为0.39±0.05 cm H2O/ml/秒。TMA-GPSA在致敏组的所有气道水平也导致伊文思蓝染料显著外渗，外周气道中的染料量显著大于气管中的染料量。此外，气道组织中伊文思蓝染料的水平随致敏后时间增加，直至测试的最晚时间点（8周）。通过ELISA检测到3、5和8周组的所有动物中均存在针对TMA-GPSA的特异性IgG1抗体，致敏后5周达到最高水平。针对TMA-GPSA的特异性IgG1滴度与TMA-GPSA激发诱导的伊文思蓝染料水平显著相关，但与RL的增加无关。
对游离TMA的皮内致敏在致敏后很长一段时间内诱导特异性气道过敏。在这个TMA诱导哮喘的动物模型中，针对变应原的特异性IgG1抗体可能影响变应原诱导的血浆渗出而非气流阻塞。
