Mould A W, Ramsay A J, Matthaei K I, Young I G, Rothenberg M E, Foster P S
Division of Biochemistry, John Curtin School of Medical Research, Australian National University, Canberra, Australia.
J Immunol. 2000 Feb 15;164(4):2142-50. doi: 10.4049/jimmunol.164.4.2142.
The mechanisms regulating the selective migration and degranulation of eosinophils in the asthmatic lung and the subsequent development of airways hyperreactivity (AHR) have not been fully delineated. In this investigation, we have employed a novel transgene model to facilitate the dissection of the contributions of IL-5 and/or eotaxin to eosinophil function in the absence of complex tissue signals derived from the allergic lung. Gene transfer of IL-5 and/or eotaxin to the lungs of naive mice induced a pronounced and selective airways eosinophilia, but did not result in eosinophil degranulation or AHR. Airways eosinophilia occurred independently of the induction of a blood eosinophilia, but was markedly augmented by the coexpression of both cytokines and/or by the transient mobilization of eosinophils from the bone marrow by the administration of i.v. IL-5. However, for eosinophil degranulation and AHR to occur, the inhalation of Ag was required in association with IL-5 and eotaxin expression. Investigations in IL-5-deficient mice linked eosinophilia, and not solely IL-5 and eotaxin, with the induction of AHR. Furthermore, eosinophil degranulation and AHR were dependent on CD4+ T cells. Importantly, this investigation shows that IL-5 regulates eosinophilia within the lung as well as in the circulation and also amplifies eotaxin-induced chemotaxis in the airway compartment. Moreover, the interplay between these cytokines, CD4+ T cells, and factors generated by Ag inhalation provides fundamental signals for eosinophil degranulation and the induction of AHR.
调节嗜酸性粒细胞在哮喘肺中选择性迁移和脱颗粒以及随后气道高反应性（AHR）发展的机制尚未完全阐明。在本研究中，我们采用了一种新型转基因模型，以在没有源自过敏性肺的复杂组织信号的情况下，便于剖析白细胞介素-5（IL-5）和/或嗜酸性粒细胞趋化因子对嗜酸性粒细胞功能的作用。将IL-5和/或嗜酸性粒细胞趋化因子基因转移至未致敏小鼠的肺中可诱导明显且选择性的气道嗜酸性粒细胞增多，但不会导致嗜酸性粒细胞脱颗粒或AHR。气道嗜酸性粒细胞增多的发生独立于血液嗜酸性粒细胞增多的诱导，但通过两种细胞因子的共表达和/或通过静脉注射IL-5使嗜酸性粒细胞从骨髓短暂动员而显著增强。然而，要发生嗜酸性粒细胞脱颗粒和AHR，则需要在IL-5和嗜酸性粒细胞趋化因子表达的同时吸入抗原（Ag）。对IL-5缺陷小鼠的研究表明，嗜酸性粒细胞增多而非仅IL-5和嗜酸性粒细胞趋化因子与AHR的诱导有关。此外，嗜酸性粒细胞脱颗粒和AHR依赖于CD4 + T细胞。重要的是，本研究表明IL-5调节肺内以及循环中的嗜酸性粒细胞增多，并且还增强气道隔室中嗜酸性粒细胞趋化因子诱导的趋化作用。此外，这些细胞因子、CD4 + T细胞与Ag吸入产生的因子之间的相互作用为嗜酸性粒细胞脱颗粒和AHR诱导提供了基本信号。
