Jones H A, Schofield J B, Krausz T, Boobis A R, Haslett C
National Heart and Lung Institute, Departments of Medicine and Histopathology, Imperial College School of Medicine, London, UK.
Am J Respir Crit Care Med. 1998 Aug;158(2):620-8. doi: 10.1164/ajrccm.158.2.9711075.
The role of inflammatory cells such as neutrophil granulocytes in the pathogenesis of pulmonary scarring is unclear. We determined the metabolic activity of neutrophils with positron emission tomography (PET) to measure regional uptake of (18F)-2-fluoro-2-deoxy-D-glucose (18FDG) following its intravenous injection. Fibrogenic or nonfibrogenic substances were instilled into the right upper lobe of rabbit lungs. Time course and intensity of the 18FDG signal in the affected region varied markedly, depending on the stimulus. Time to peak signal (Tmax) and rate constant for its decline (k) for the test substances were, respectively: C5a 10 h (Tmax), 0.045 +/- 0.030 h-1 (k); Streptococcus pneumoniae 15 h, 0.068 +/- 0.012 h-1; bleomycin 28 h, 0.002 +/- 0.001 h-1; microcrystalline silica (microXSiO2), 90 h, 0.0012 +/- 0.0007 h-1; amorphous silica (aSiO2), no response. Response to the nonfibrogenic agents C5a, S. pneumoniae and aSiO2 was brief or nonexistent, falling to baseline values within 3 d, whereas that to the fibrogenic agents bleomycin and microXSiO2 persisted for up to 4 wk. Neutrophil numbers in the lung were proportional to the 18FDG signal following C5a and S. pneumoniae, but not bleomycin and microXSiO2. Autoradiography of lungs following administration of (3H)-deoxyglucose [(3H)-DG] showed specific localization to neutrophils in all models. Thus, 18FDG uptake provides a remarkably specific measure of neutrophil activity in situ, and the development of pulmonary fibrosis may be related to persistence of this activity.
中性粒细胞等炎症细胞在肺瘢痕形成发病机制中的作用尚不清楚。我们通过正电子发射断层扫描（PET）测定中性粒细胞的代谢活性，以测量静脉注射（18F）-2-氟-2-脱氧-D-葡萄糖（18FDG）后的区域摄取情况。将致纤维化或非致纤维化物质注入兔肺右上叶。根据刺激因素的不同，受影响区域18FDG信号的时间进程和强度有显著差异。测试物质的信号峰值时间（Tmax）及其下降速率常数（k）分别为：C5a为10小时（Tmax），0.045±0.030 h-1（k）；肺炎链球菌为15小时，0.068±0.012 h-1；博来霉素为28小时，0.002±0.001 h-1；微晶硅（microXSiO2）为90小时，0.0012±0.0007 h-1；无定形硅（aSiO2）无反应。对非致纤维化剂C5a、肺炎链球菌和aSiO2的反应短暂或不存在，在3天内降至基线值，而对致纤维化剂博来霉素和microXSiO2的反应持续长达4周。C5a和肺炎链球菌作用后，肺内中性粒细胞数量与18FDG信号成正比，但博来霉素和microXSiO2作用后并非如此。给予（3H）-脱氧葡萄糖[（3H）-DG]后对肺进行放射自显影显示，在所有模型中均有中性粒细胞的特异性定位。因此，18FDG摄取为原位中性粒细胞活性提供了一种非常特异的测量方法，肺纤维化的发展可能与这种活性的持续存在有关。
