Carbon in airway macrophages from children with asthma

被引:29
作者
Brugha, Rossa E. [1 ]
Mushtaq, Naseem [1 ]
Round, Thomas [1 ]
Gadhvi, Dev H. [1 ]
Dundas, Isobel [1 ]
Gaillard, Erol [2 ]
Koh, Lee [1 ]
Fleming, Louise J. [3 ]
Lewis, Daniel J. [4 ]
Sanak, Marek [5 ]
Wood, Helen E. [6 ]
Barratt, Benjamin [6 ]
Mudway, Ian S. [6 ]
Kelly, Frank J. [6 ]
Griffiths, Christopher J. [1 ]
Grigg, Jonathan [1 ]
机构
[1] Univ London, Blizard Inst, London E1 2AT, England
[2] Univ Hosp Leicester, Dept Infect Immun & Inflammat, Leicester, Leics, England
[3] Univ London Imperial Coll Sci Technol & Med, Dept Resp Paediat, London, England
[4] Univ London London Sch Hyg & Trop Med, Dept Social & Environm Hlth Res, London WC1E 7HT, England
[5] Jagiellonian Univ, Sch Med, Dept Med, Krakow, Poland
[6] Kings Coll London, Sch Biomed Sci, MRC PHE Ctr Environm & Hlth, London WC2R 2LS, England
关键词
PROSTAGLANDIN E-2; ALVEOLAR MACROPHAGES; DIESEL EXHAUST; PHAGOCYTOSIS; PARTICLES; EXPOSURE; ASSOCIATION; DEPOSITION; SEVERITY; CELLS;
D O I
10.1136/thoraxjnl-2013-204734
中图分类号
R56 [呼吸系及胸部疾病];
学科分类号
100201 [内科学];
摘要
Background Airway macrophage (AM) phagocytosis is impaired in severe asthma. Prostaglandin (PG) E-2 and D-2 are increased in severe asthma and suppress AM phagocytic function in vitro. In this study, we sought evidence for PG-mediated impairment of phagocytosis of inhalable carbonaceous particulate matter (PM) by AM in children with severe asthma compared with mild asthmatics and healthy controls. Methods AM were obtained from children with asthma and healthy controls using induced sputum. AM carbon area (mu m(2)) was assessed by image analysis. In a subgroup of asthmatics, urinary PGE(2) and PGD(2) metabolites were measured by high-performance liquid chromatography, and PM exposure at the home address was modelled. Phagocytosis of PM by human monocyte-derived macrophages and rat AM was assessed in vitro by image analysis. Results AM carbon was 51% lower in children with moderate-to-severe asthma (n=36) compared with mild asthmatics (n=12, p<0.01) and healthy controls (n=47, p<0.01). There was no association between modelled PM exposure and AM carbon in 33 asthmatics who had a urine sample, but there was an inverse association between AM carbon and urinary metabolites of PGE(2) and D-2 (n=33, rs=-0.40, p<0.05, and rs=-0.44, p<0.01). PGE(2) 10(-6) M, but not PGD(2) 10(-6) M, suppressed phagocytosis of PM10 by human macrophages in vitro (p<0.05 vs control). PGE(2) 10(-6) M also suppressed phagocytosis of PM10 by rat AM in vitro (p<0.01 vs control). Conclusions Phagocytosis of inhaled carbonaceous PM by AMs is impaired in severe asthma. PGE(2) may contribute to impaired AM phagocytic function in severe asthma.
引用
收藏
页码:654 / 659
页数:6
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