Hogaboam C M, Gallinat C S, Taub D D, Strieter R M, Kunkel S L, Lukacs N W
Departments ofPathology and Internal Medicine, Division of Pulmonary and Critical Care, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
J Immunol. 1999 May 15;162(10):6071-9.
The immunomodulatory role of the chemokine C10 was explored in allergic airway responses during experimental allergic bronchopulmonary aspergillosis (ABPA). The intratracheal delivery of Asperigillus fumigatus Ag into A. fumigatus-sensitized mice resulted in significantly increased levels of C10 within the bronchoalveolar lavage, and these levels peaked at 48 h after A. fumigatus challenge. In addition, C10 levels in BAL samples were greater than 5-fold higher than levels of other chemokines such as monocyte-chemoattractant protein-1, eotaxin, and macrophage-inflammatory protein-1alpha. From in vitro studies, it was evident that major pulmonary sources of C10 may have included alveolar macrophages, lung fibroblasts, and vascular smooth muscle cells. Experimental ABPA was associated with severe peribronchial eosinophilia, bronchial hyperresponsiveness, and augmented IL-13 and IgE levels. The immunoneutralization of C10 with polyclonal anti-C10 antiserum 2 h before the intratracheal A. fumigatus challenge significantly reduced the airway inflammation and hyperresponsiveness in this model of ABPA, but had no effect on IL-10 nor IgE levels. Taken together, these data suggest that C10 has a unique role in the progression of experimental ABPA.
在实验性变应性支气管肺曲霉病(ABPA)期间,研究了趋化因子C10在变应性气道反应中的免疫调节作用。将烟曲霉抗原经气管内注入对烟曲霉致敏的小鼠,导致支气管肺泡灌洗中C10水平显著升高,且这些水平在烟曲霉攻击后48小时达到峰值。此外,支气管肺泡灌洗样本中C10水平比其他趋化因子如单核细胞趋化蛋白-1、嗜酸性粒细胞趋化因子和巨噬细胞炎性蛋白-1α的水平高5倍以上。体外研究表明,C10的主要肺来源可能包括肺泡巨噬细胞、肺成纤维细胞和血管平滑肌细胞。实验性ABPA与严重的支气管周围嗜酸性粒细胞增多、支气管高反应性以及IL-13和IgE水平升高有关。在经气管内注入烟曲霉攻击前2小时,用多克隆抗C10抗血清对C10进行免疫中和,可显著减轻该ABPA模型中的气道炎症和高反应性,但对IL-10和IgE水平无影响。综上所述,这些数据表明C10在实验性ABPA的进展中具有独特作用。