Impaired alveolar macrophage response to haemophilus antigens in chronic obstructive lung disease
Impaired alveolar macrophage response to haemophilus antigens in chronic obstructive lung disease
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DOI：
10.1164/rccm.200509-1461oc
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发表时间：
2006-07-01
影响因子：
24.7
通讯作者：
Sethi, Sanjay
中科院分区：
文献类型：
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作者：
Berenson, Charles S.;Wrona, Catherine T.;Sethi, Sanjay
原理：非分型流感嗜血杆菌(NTHI)与巨噬细胞的相互作用与慢性阻塞性肺疾病(COPD)的发病机制有关。然而，介导NTHI-巨噬细胞炎症的免疫学机制却知之甚少。NTHI的外膜蛋白(OMP)P6和脂寡糖(LOS)是强有力的免疫调节剂。目的：为了验证这一假设，我们从COPD吸烟者、非COPD吸烟者和非吸烟者的肺泡巨噬细胞和血巨噬细胞分别与纯化的LOS和OMP P6以及OMP P2和总外膜制剂(0.1-1微克/毫升)孵育。方法：测定培养上清液(24 H)中IL-1β、TNF-α、IL-1β、IL-12、IL-1β和OMP P6。结果：LOS和OMP P6对COPD和非COPD肺泡巨噬细胞的诱导作用比较显示，COPD肺泡巨噬细胞对IL-8、TNF-α和IL-1β的反应明显减弱(P<0.05)。
Rationale: Interactions of nontypeable Haemophilus influenzae (NTHI) with macrophages are implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD). However, the immunologic mechanisms that mediate NTHI-macrophage inflammation are poorly understood. Outer membrane protein (OMP) P6 and lipooligosaccharide (LOS) of NTHI are potent immunomodulators. We theorized that alveolar macrophages in COPD possess fundamental immune defects that permit NTHI to evade host responses.Objective: To test this hypothesis, we obtained human alveolar and blood macrophages from exsmokers with COPD, exsmokers without COPD, and nonsmokers.Methods: Alveolar and blood macrophages from each donor were incubated with purified LOS and OMP P6 and with OMP P2 and the total outer membrane preparation (0.1-1 mu g/ml).Measurements: Supernatants (24 h) were assayed for IL-1 beta, TNF-alpha, IL-1 beta, IL-12, and IL-8 by multianalyte multiplexed flow cytometry.Results: Comparative induction of COPD and non-COPD alveolar macrophages by LOS and OMP P6 revealed diminished IL-8, TNF-alpha, and IL-1 beta responses of COPD alveolar macrophages (p