Baharom Faezzah, Thomas Saskia, Rankin Gregory, Lepzien Rico, Pourazar Jamshid, Behndig Annelie F, Ahlm Clas, Blomberg Anders, Smed-Sörensen Anna
Immunology and Allergy Unit, Department of Medicine, Solna, Karolinska Institutet, 171 76 Stockholm, Sweden;
Division of Medicine, Department of Public Health and Clinical Medicine, Umeå University, 901 85 Umeå, Sweden; and.
J Immunol. 2016 Jun 1;196(11):4498-509. doi: 10.4049/jimmunol.1600071. Epub 2016 May 2.
Every breath we take contains potentially harmful pathogens or allergens. Dendritic cells (DCs), monocytes, and macrophages are essential in maintaining a delicate balance of initiating immunity without causing collateral damage to the lungs because of an exaggerated inflammatory response. To document the diversity of lung mononuclear phagocytes at steady-state, we performed bronchoscopies on 20 healthy subjects, sampling the proximal and distal airways (bronchial wash and bronchoalveolar lavage, respectively), as well as mucosal tissue (endobronchial biopsies). In addition to a substantial population of alveolar macrophages, we identified subpopulations of monocytes, myeloid DCs (MDCs), and plasmacytoid DCs in the lung mucosa. Intermediate monocytes and MDCs were highly frequent in the airways compared with peripheral blood. Strikingly, the density of mononuclear phagocytes increased upon descending the airways. Monocytes from blood and airways produced 10-fold more proinflammatory cytokines than MDCs upon ex vivo stimulation. However, airway monocytes were less inflammatory than blood monocytes, suggesting a more tolerant nature. The findings of this study establish how to identify human lung mononuclear phagocytes and how they function in normal conditions, so that dysregulations in patients with respiratory diseases can be detected to elucidate their contribution to immunity or pathogenesis.
我们吸入的每一口空气都可能含有有害病原体或过敏原。树突状细胞(DC)、单核细胞和巨噬细胞对于维持一种微妙的平衡至关重要,即启动免疫反应,同时又不会因过度的炎症反应而对肺部造成附带损害。为了记录稳态下肺单核吞噬细胞的多样性,我们对20名健康受试者进行了支气管镜检查,分别对近端和远端气道(分别为支气管冲洗和支气管肺泡灌洗)以及黏膜组织(支气管内活检)进行采样。除了大量的肺泡巨噬细胞外,我们在肺黏膜中还鉴定出了单核细胞、髓样DC(MDC)和浆细胞样DC的亚群。与外周血相比,中间单核细胞和MDC在气道中更为常见。令人惊讶的是,单核吞噬细胞的密度在气道下行时增加。体外刺激后,血液和气道中的单核细胞产生的促炎细胞因子比MDC多10倍。然而,气道单核细胞的炎症程度低于血液单核细胞,表明其具有更强的耐受性。这项研究的结果确定了如何识别人类肺单核吞噬细胞以及它们在正常情况下的功能,以便能够检测出呼吸系统疾病患者的失调情况,从而阐明它们对免疫或发病机制的作用。