Phagocytic Dysfunction of Human Alveolar Macrophages and Severity of Chronic Obstructive Pulmonary Disease
Phagocytic Dysfunction of Human Alveolar Macrophages and Severity of Chronic Obstructive Pulmonary Disease
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DOI：
10.1093/infdis/jit400
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发表时间：
2013-12-15
影响因子：
6.4
通讯作者：
Sethi, Sanjay
中科院分区：
文献类型：
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作者：
Berenson, Charles S.;Kruzel, Ragina L.;Sethi, Sanjay
背景慢性阻塞性肺疾病（COPD）患者肺泡巨噬细胞对不可分型流感嗜血杆菌（NTHI）的吞噬功能存在根本性损害。然而，不同的呼吸道病原体之间的功能障碍的吞噬作用的相对选择性：NTHI，卡他莫拉菌（MC），肺炎链球菌（SP），和非细菌颗粒，以及受损的吞噬作用的COPD的严重程度的贡献，还没有探索。将从非吸烟者（n = 20）、COPD戒烟者（n = 32）和COPD活跃吸烟者（n = 64）获得的肺泡巨噬细胞与标记的NTHI、MC、SP和荧光微球一起孵育。吞噬作用以每种细胞的细胞内百分比来测量。COPD戒烟者和活跃吸烟者的肺泡巨噬细胞对NTHI（P = .003）和MC（P = .0007）的补体非依赖性吞噬功能受损，但对SP或微球的吞噬功能无影响。尽管如此，各组内补体介导的吞噬作用仅对SP增强。在COPD活跃吸烟者（P < .0001）和戒烟者（P = .028）中，NTHI的吞噬功能缺陷显著大于MC。此外，COPD的严重程度（FEV1%预测值）与AM对NTHI（P = 0.0016）和MC（P = 0.01）的吞噬功能受损相关。这些研究描述了COPD中缺陷性肺泡巨噬细胞吞噬呼吸道细菌的病原体和宿主特异性差异，进一步阐明了COPD中细菌持续存在的免疫学基础，并首次证明了吞噬功能受损与疾病严重程度的相关性。
Background. Alveolar macrophages in chronic obstructive pulmonary disease (COPD) have fundamental impairment of phagocytosis for nontypeable Haemophilus influenzae (NTHI). However, relative selectivity of dysfunctional phagocytosis among diverse respiratory pathogens: NTHI, Moraxella catarrhalis (MC), Streptococcus pneumoniae (SP), and nonbacterial particles, as well as the contribution of impaired phagocytosis to severity of COPD, has not been explored.Methods. Alveolar macrophages, obtained from nonsmokers (n = 20), COPD ex-smokers (n = 32), and COPD active smokers (n = 64), were incubated with labeled NTHI, MC, SP, and fluorescent microspheres. Phagocytosis was measured as intracellular percentages of each.Results. Alveolar macrophages of COPD ex-smokers and active smokers had impaired complement-independent phagocytosis of NTHI (P = .003) and MC (P = .0007) but not SP or microspheres. Nonetheless, complement-mediated phagocytosis was enhanced within each group only for SP. Defective phagocytosis was significantly greater for NTHI than for MC among COPD active smokers (P < .0001) and ex-smokers (P = .028). Moreover, severity of COPD (FEV1% predicted) correlated with impaired AM phagocytosis for NTHI (P = .0016) and MC (P = .01).Conclusions. These studies delineate pathogen-and host-specific differences in defective alveolar macrophages phagocytosis of respiratory bacteria in COPD, further elucidating the immunologic basis for bacterial persistence in COPD and provide the first demonstration of association of impaired phagocytosis to severity of disease.