Fitzpatrick Anne M, Holguin Fernando, Teague W Gerald, Brown Lou Ann S
Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA.
J Allergy Clin Immunol. 2008 Jun;121(6):1372-8, 1378.e1-3. doi: 10.1016/j.jaci.2008.03.008. Epub 2008 Apr 16.
Lower respiratory tract infection is a differentiating feature of children with poorly controlled asthma.
Given the role of alveolar macrophages (AMs) in innate immunity, we hypothesized that AM phagocytosis might be impaired in poorly controlled asthma.
Bronchoalveolar lavage fluid AMs were isolated from 28 asthmatic children (moderate asthma, n = 12; severe asthma, n = 16), 10 nonasthmatic children with chronic cough treated with inhaled corticosteroids, and 10 healthy adult control subjects. AMs were stimulated with LPS and exposed to fluorescein isothiocyanate-conjugated Staphylococcus aureus for 2 hours. Phagocytosis was quantified by using a phagocytic index (PI) calculated from the percentage of phagocytic cells multiplied by the relative fluorescence (RFU) units of S. aureus per cell. Apoptosis was determined from the percentage of cells positive for poly (adenosine diphosphate-ribose) polymerase.
Phagocytosis as measured by using the unstimulated PI was decreased in subjects with poorly controlled asthma (healthy control subjects, 9330 +/- 3992 RFU; chronic cough, 9042 +/- 5976 RFU; moderate asthma, 4361 +/- 2536 RFU; severe asthma, 3153 +/- 1886 RFU; P < .001) and remained unchanged with LPS stimulation. Children with severe asthma also had increased AM apoptosis, both the unstimulated and LPS-simulated states (P < .001), which correlated with the PI.
AM function is compromised in children with poorly controlled asthma and is characterized by decreased phagocytosis and increased apoptosis.
下呼吸道感染是哮喘控制不佳患儿的一个鉴别特征。
鉴于肺泡巨噬细胞(AM)在先天免疫中的作用,我们推测在哮喘控制不佳时AM吞噬功能可能受损。
从28例哮喘患儿(中度哮喘,n = 12;重度哮喘,n = 16)、10例接受吸入性糖皮质激素治疗的慢性咳嗽非哮喘患儿以及10例健康成人对照受试者中分离支气管肺泡灌洗液中的AM。用脂多糖刺激AM,并使其暴露于异硫氰酸荧光素偶联的金黄色葡萄球菌中2小时。通过吞噬指数(PI)对吞噬作用进行定量,PI由吞噬细胞百分比乘以每个细胞金黄色葡萄球菌的相对荧光(RFU)单位计算得出。通过聚(二磷酸腺苷-核糖)聚合酶阳性细胞的百分比来确定细胞凋亡情况。
哮喘控制不佳的受试者中,未刺激状态下测量的吞噬作用降低(健康对照受试者,9330±3992 RFU;慢性咳嗽,9042±5976 RFU;中度哮喘,4361±2536 RFU;重度哮喘,3153±1886 RFU;P <.001),且脂多糖刺激后保持不变。重度哮喘患儿在未刺激和脂多糖刺激状态下的AM凋亡均增加(P <.001),且与PI相关。
哮喘控制不佳的患儿AM功能受损,其特征为吞噬作用降低和凋亡增加。