Granulocyte-macrophage colony-stimulating factor and lung immunity in pulmonary alveolar proteinosis
Granulocyte-macrophage colony-stimulating factor and lung immunity in pulmonary alveolar proteinosis
复制标题
DOI：
10.1164/rccm.200406-716oc
复制
发表时间：
2005-05-15
影响因子：
24.7
通讯作者：
Nukiwa, T
中科院分区：
文献类型：
--
作者：
Tazawa, R;Hamano, E;Nukiwa, T
抗粒细胞-巨噬细胞集落刺激因子（GM-CSF）自身抗体被推断为引起特发性肺泡蛋白沉积症（iPAP）：该抗体中和GM-CSF，从而损害肺泡巨噬细胞的分化。施用GM-CSF改善患有iPAP的患者的呼吸功能，如在使用雾化的GM-CSF的该研究中所证实的。为了阐明其机制，我们对从三名成功接受雾化GM-CSF治疗的iPAP患者中获得的支气管肺泡灌洗液和肺泡巨噬细胞进行了表征。肺泡巨噬细胞的细胞数、表面甘露糖受体和转录因子PU.1的表达以及吞噬能力均恢复至对照水平。随着治疗，GM-CSF活性的中和能力显著降低，伴随着自身抗体水平的降低。有趣的是，GMCSF自身抗体复合物的量也减少。在分析复合物的一种情况下，结合复合物的大多数GM-CSF是内源性蛋白质，表明复合物在治疗后立即从肺中除去。我们的研究表明，GM-CSF管理引起对蛋白质在肺中和能力的下降。因此，它有助于恢复肺泡巨噬细胞的正常功能。
The anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibody is inferred to cause idiopathic pulmonary alveolar proteinosis (iPAP): the antibody neutralizes GM-CSF and thereby impairs differentiation of alveolar macrophages. Administration of GM-CSF improves respiratory function of patients with iPAP, as confirmed in this study using aerosolized GM-CSF. To elucidate its mechanism, we characterized bronchoalveolar lavage fluid and alveolar macrophages obtained from three patients with iPAP who were treated successfully with aerosolized GM-CSF. Cell number, expressions of surface mannose receptor and the transcription factor PU.1, and phagocytic ability of alveolar macrophages were all restored to control levels. With treatment, the neutralizing capacity of GM-CSF activity was reduced markedly, concomitant with the decreasing autoantibody levels. Interestingly, the amount of GMCSF autoantibody complex also decreased. In one case in which the complex was analyzed, the majority of GM-CSF binding the complex was endogenous protein, suggesting that the complex is removed immediately from the lung after treatment. Our study shows that GM-CSF administration engenders a decrease in the neutralizing capacity against the protein in the lungs. Thereby, it facilitates restoration of the normal function of alveolar macrophages.