气道内吞噬细胞可吞噬吸入性的颗粒物质,有助于清除肺内潜在的有毒物质(包括空气中的一些粉尘致敏原),是气道内的主要防御机制。因气道内单核细胞和巨噬细胞也有抗原递呈细胞的功能,其可吸附吞噬气道表面颗粒物质的能力对于过敏性哮喘患者的意义则显得更为突出。为明确是否过敏性哮喘患者气道内单核巨噬细胞的吞噬细胞活性更强, Lay等人选择了10例轻度过敏性哮喘患者和8例健康对照人群,比较两组人群吸入放射性物质标记的颗粒粉尘后体内单核巨噬细胞的吞噬功能。入选人群吸入含有放射性物质胶体硫标记的颗粒,2小时后取其诱导痰进行检测,看浮于表面的和进入细胞内的放射性物质的比率以评价吞噬细胞功能。所有人在进行诱导痰之前均给予沙丁胺醇治疗。所有受试人群的呼吸模式(及深度)均进行标准化训练,以使其支气管内气溶胶分布沉积无差异性。
实验结果表明哮喘患者气道细胞摄取颗粒明显较健康人要多(57.2% (95% CI 46.5% to 67.9%) vs 22.3% (95% CI 4.9% to 39.6%), p<0.01),与体外吞噬细胞功能相同。哮喘患者痰中单核巨噬细胞的比率与吸附吞噬颗粒的比例呈明显正相关(r = 0.85, p<0.01),而健康对照组中此相关性不明显。
Lay的实验说明轻度哮喘患者的气道内巨噬细胞吸附吞噬粉尘颗粒的能力明显增强。分析这种增强的吞噬能力以及对颗粒性(过敏性)抗原的处理能力可能是导致过敏性气道疾病的一个原因,参与其发病机制和疾病的进展,可能增加与过敏原或颗粒暴露有关的哮喘发作风险。
(于娜 中国医科大学附属第一医院呼吸内科 110001 摘译)
(Thorax 2009;64:313-320 )
Thorax 2009;64:313-320
In vivo uptake of inhaled particles by airway phagocytes is enhanced in patients with mild asthma compared with normal volunteers
J C Lay1,2, N E Alexis1,2, K L Zeman1, D B Peden1,2,3 and W D Bennett1,3
Background: The uptake of inhaled particulate matter by airway phagocytes is an important defence mechanism contributing to the clearance of potentially toxic substances, including aeroallergens, from the lung. Since airway monocytes and macrophages can also function as antigen presenting cells, their ability to engulf materials deposited on the airway surface is of particular interest in patients with allergic asthma. To determine whether airway mononuclear phagocytes of patients with allergic asthma might have enhanced phagocytic activity, the in vivo uptake of inhaled radiolabelled particles was compared in 10 patients with mild allergic asthma and 8 healthy (non-allergic) individuals.
Methods: Phagocyte function was assessed by quantifying the proportion of radioactivity associated with cellular and supernatant fractions of induced sputum 2 h after inhalation of radiolabelled sulfur colloid particles. All subjects were pretreated with albuterol before sputum induction. A standardised breathing pattern was used to target aerosol deposition in the bronchial airways.
Results: In vivo particle uptake by airway cells was significantly greater in patients with asthma than in healthy volunteers (57.2% (95% CI 46.5% to 67.9%) vs 22.3% (95% CI 4.9% to 39.6%), p<0.01), as was in vitro phagocytosis of opsonised zymosan-A bioparticles. There was also a significant correlation (r = 0.85, p<0.01) between the percentage of sputum mononuclear phagocytes and the percentage uptake of particles in the patients with asthma but not in the control subjects.
Conclusions: In vivo particle uptake by airway macrophages is enhanced in persons with mild asthma. Enhanced uptake and processing of particulate antigens could contribute to the pathogenesis and progression of allergic airways disease and may contribute to the increased risk of disease exacerbation associated with particulate exposure.