Itami D M, Oshiro T M, Araujo C A, Perini A, Martins M A, Macedo M S, Macedo-Soares M F
Laboratory of Immunopathology, Butantan Institute, São Paulo, Brazil.
Clin Exp Allergy. 2005 Jul;35(7):873-9. doi: 10.1111/j.1365-2222.2005.02268.x.
We have recently isolated two distinct components from Ascaris suum adult worms with different effects on the immune system: the allergenic protein of A. suum (APAS-3), which induces IgE antibody production, and suppressive protein of A. suum (PAS-1), which inhibits humoral and cellular immune responses induced by unrelated antigens. In this study, we investigated the immunomodulatory effect of PAS-1 on a murine model of asthma induced by APAS-3.
BALB/c mice were immunized twice with APAS-3 or APAS-3 plus PAS-1 by the intraperitoneal and subcutaneous route (on days 0 and 7) and challenged twice with the same antigens intranasally (days 14 and 21). Two days after the last challenge, the allergic airway inflammation was evaluated by cellular migration, eosinophil peroxidase (EPO) activity, cytokine and chemokine production and pulmonary mechanical parameters.
The allergenic properties of APAS-3 were confirmed by the stimulation of anaphylactic IgE and IgG1 antibody production and eosinophilic airway inflammation and hyper-responsiveness. On the other hand, PAS-1-treated mice showed a marked suppression of cellular migration and EPO activity that correlated well with a significant reduction in the levels of IL-4, IL-5, eotaxin and RANTES in the bronchoalveolar lavage (BAL) fluid. In contrast, considerable amounts of IL-10 were observed in the BAL fluid of PAS-1-treated mice. Airway hyper-responsiveness was obtained in APAS-3-immunized mice, but the conductance of the respiratory system was restored to normal values in the presence of PAS-1.
These results indicate that A. suum allergenic protein APAS-3 induces a T helper 2-type immune response and, consequently, eosinophilic airway inflammation and hyper-responsiveness. Moreover, the modulatory protein PAS-1 has a marked suppressive effect on this response, and the inhibition of cytokine (IL-4, IL-5) and chemokine (eotaxin and RANTES) release, probably because of the presence of IL-10, may contribute to this effect.
我们最近从猪蛔虫成虫中分离出两种对免疫系统有不同作用的不同成分：猪蛔虫变应原蛋白（APAS - 3），可诱导IgE抗体产生；猪蛔虫抑制蛋白（PAS - 1），可抑制无关抗原诱导的体液免疫和细胞免疫反应。在本研究中，我们研究了PAS - 1对由APAS - 3诱导的小鼠哮喘模型的免疫调节作用。
BALB/c小鼠通过腹腔和皮下途径（在第0天和第7天）用APAS - 3或APAS - 3加PAS - 1免疫两次，并通过鼻内途径用相同抗原攻击两次（第14天和第21天）。最后一次攻击后两天，通过细胞迁移、嗜酸性粒细胞过氧化物酶（EPO）活性、细胞因子和趋化因子产生以及肺力学参数评估过敏性气道炎症。
APAS - 3的变应原特性通过刺激过敏性IgE和IgG1抗体产生以及嗜酸性气道炎症和高反应性得到证实。另一方面，用PAS - 1处理的小鼠显示细胞迁移和EPO活性明显受到抑制，这与支气管肺泡灌洗（BAL）液中IL - 4、IL - 5、嗜酸性粒细胞趋化因子和调节激活正常T细胞表达和分泌的趋化因子水平的显著降低密切相关。相反，在PAS - 1处理的小鼠的BAL液中观察到大量IL - 10。在APAS - 3免疫的小鼠中出现气道高反应性，但在存在PAS - 1的情况下呼吸系统的传导恢复到正常值。
这些结果表明，猪蛔虫变应原蛋白APAS - 3诱导辅助性T细胞2型免疫反应，因此导致嗜酸性气道炎症和高反应性。此外，调节蛋白PAS - 1对这种反应有明显的抑制作用，细胞因子（IL - 4、IL - 5）和趋化因子（嗜酸性粒细胞趋化因子和调节激活正常T细胞表达和分泌的趋化因子）释放的抑制，可能由于IL - 10的存在，可能有助于这种作用。
