Calheiros A S, Aguiar Pires A L, Pereira da Silva J, Cordeiro R S, Martins M A, Lima M C
Departamento de Fisiologia e Farmacodinâmica, Instituto Oswaldo Cruz - IOC/FIOCRUZ, Rio de Janeiro, Brasil.
Int Arch Allergy Immunol. 2001 Dec;126(4):325-34. doi: 10.1159/000049530.
In this study, we postulated that repeated cycles of IgE passive sensitisation and antigen challenge may play a role in up-regulating eosinophil response in allergic conditions. Antigen-mediated stimulation of the pleural cavity of rats passively sensitised with a single injection of IgE anti-DNP resulted in mast cell degranulation, increase in vascular permeability and mild neutrophilia, but no pleural eosinophilia. In contrast, a second cycle of sensitisation and challenge, performed within 7 days, showed a marked eosinophilia in parallel with a lower plasma leakage and comparable neutrophilia. The eosinophilic phenomenon was not reproduced when (1) IgE sensitisation or antigen challenge was omitted in the first cycle, or (2) the first cycle was replaced by either a histamine and 5-HT dual challenge or a PAF challenge. Furthermore, we found an increase in eotaxin levels in animals subjected to two rather than one cycle of sensitisation and challenge. Treatment with the PAF receptor antagonist BN 52021 or with the lipoxygenase inhibitor zileuton, but not mast cell granule depletion, prevented the allergen-evoked eosinophil accumulation in rechallenged animals. Our results indicate that repeated cycles of IgE-driven inflammation may lead to eosinophil accumulation in a mechanism dependent on eotaxin, PAF and leukotrienes.
在本研究中,我们推测IgE被动致敏和抗原激发的重复循环可能在过敏性疾病中上调嗜酸性粒细胞反应方面发挥作用。用单次注射IgE抗DNP被动致敏的大鼠胸腔经抗原介导刺激后,导致肥大细胞脱颗粒、血管通透性增加和轻度中性粒细胞增多,但无胸腔嗜酸性粒细胞增多。相比之下,在7天内进行的第二次致敏和激发循环显示出明显的嗜酸性粒细胞增多,同时血浆渗漏减少且中性粒细胞增多程度相当。当(1)在第一个循环中省略IgE致敏或抗原激发,或(2)第一个循环被组胺和5-HT双重激发或PAF激发替代时,嗜酸性粒细胞现象未重现。此外,我们发现经历两个而非一个致敏和激发循环的动物中嗜酸性粒细胞趋化因子水平升高。用PAF受体拮抗剂BN 52021或脂氧合酶抑制剂齐留通治疗,但不是肥大细胞颗粒耗竭,可防止再次激发动物中变应原诱发的嗜酸性粒细胞积聚。我们的结果表明,IgE驱动的炎症重复循环可能通过依赖嗜酸性粒细胞趋化因子、PAF和白三烯的机制导致嗜酸性粒细胞积聚。