Blizard Institute, Queen Mary, University of London, London, UK.
Department of Infection, Immunity and Inflammation, University Hospitals of Leicester, Leicester, UK.
Thorax. 2014 Jul;69(7):654-9. doi: 10.1136/thoraxjnl-2013-204734. Epub 2014 Feb 24.
Airway macrophage (AM) phagocytosis is impaired in severe asthma. Prostaglandin (PG) E2 and D2 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.
AM were obtained from children with asthma and healthy controls using induced sputum. AM carbon area (μm(2)) was assessed by image analysis. In a subgroup of asthmatics, urinary PGE2 and PGD2 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.
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 PGE2 and D2 (n=33, rs=-0.40, p<0.05, and rs=-0.44, p<0.01). PGE2 10(-6) M, but not PGD2 10(-6) M, suppressed phagocytosis of PM10 by human macrophages in vitro (p<0.05 vs control). PGE2 10(-6) M also suppressed phagocytosis of PM10 by rat AM in vitro (p<0.01 vs control).
Phagocytosis of inhaled carbonaceous PM by AMs is impaired in severe asthma. PGE2 may contribute to impaired AM phagocytic function in severe asthma.
气道巨噬细胞（AM）吞噬作用在严重哮喘中受损。前列腺素（PG）E2 和 D2 在严重哮喘中增加，并在体外抑制 AM 的吞噬功能。在这项研究中，我们试图证明 PG 介导的严重哮喘儿童 AM 对可吸入碳质颗粒物（PM）的吞噬作用受损，与轻度哮喘和健康对照相比。
使用诱导痰从哮喘儿童和健康对照中获得 AM。通过图像分析评估 AM 碳面积（μm2）。在哮喘患者的亚组中，通过高效液相色谱法测量尿 PG E2 和 PGD2 代谢物，并对家庭住址的 PM 暴露进行建模。通过图像分析评估人单核细胞衍生的巨噬细胞和大鼠 AM 对 PM 的体外吞噬作用。
与轻度哮喘者（n=12，p<0.01）和健康对照者（n=47，p<0.01）相比，中重度哮喘儿童（n=36）的 AM 碳含量低 51%。在 33 名有尿液样本的哮喘患者中，模型化的 PM 暴露与 AM 碳之间没有关联，但 AM 碳与 PG E2 和 D2 的尿代谢物之间存在负相关（n=33，rs=-0.40，p<0.05，和 rs=-0.44，p<0.01）。PG E210（-6）M，但不是 PGD210（-6）M，抑制了 PM10 在体外对人巨噬细胞的吞噬作用（p<0.05 与对照相比）。PG E210（-6）M 也抑制了 PM10 在体外对大鼠 AM 的吞噬作用（p<0.01 与对照相比）。
AM 对吸入碳质 PM 的吞噬作用在严重哮喘中受损。PG E2 可能导致严重哮喘中 AM 吞噬功能受损。
