Pulmonary fibrosis correlates with duration of tissue neutrophil activation
Pulmonary fibrosis correlates with duration of tissue neutrophil activation
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DOI：
10.1164/ajrccm.158.2.9711075
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发表时间：
1998-08-01
影响因子：
24.7
通讯作者：
Haslett, C
中科院分区：
文献类型：
--
作者：
Jones, HA;Schofield, JB;Haslett, C
中性粒细胞等炎症细胞在肺部疤痕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，以测量静脉注射后 (F-18)-2-氟-2-脱氧-D-葡萄糖 ((18)FDG) 的区域摄取。将纤维化或非纤维化物质注入兔肺的右上叶。受影响区域的 (18)FDG 信号的时间进程和强度根据刺激的不同而显着变化。测试物质的峰值信号时间 (T-max) 及其下降速率常数 (k) 分别为：C5a 10 小时 (T-max)、0.045 +/- 0.030 小时(-1) (k)；肺炎链球菌15小时，0.068+/-0.012小时(-1)；博来霉素 28 小时，0.002 +/- 0.001 小时(-1)；微晶二氧化硅 (mu XSiO2)，90 小时，0.0012 +/- 0.0007 小时(-1)；无定形二氧化硅 (aSiO(2))，无反应。对非纤维形成剂 C5a、肺炎链球菌和 aSiO(2) 的反应短暂或不存在，在 3 天内降至基线值，而对纤维形成剂博来霉素和 mu XSiO2 的反应持续长达 4 周。肺中的中性粒细胞数量与 C5a 和肺炎链球菌后的 (18)FDG 信号成正比，但与博莱霉素和 mu XSiO2 不成正比。施用(H-3)-脱氧葡萄糖[(H-3)-DC]后的肺部放射自显影显示所有模型中中性粒细胞的特异性定位。因此，(18)FDG摄取提供了中性粒细胞原位活性的非常具体的测量，并且肺纤维化的发展可能与该活性的持续存在有关。
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 (F-18)-2-fluoro-2-deoxy-D-glucose ((18)FDG) following its intravenous injection. Fibrogenic or nonfibrogenic substances were instilled into the right upper lobe of rabbit lungs. Time course and intensity of the (18)FDG signal in the affected region varied markedly, depending on the stimulus. Time to peak signal (T-max) and rate constant for its decline (k) for the test substances were, respectively: C5a 10 h (T-max), 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 (mu XSiO2), 90 h, 0.0012 +/- 0.0007 h(-1); amorphous silica (aSiO(2)), no response. Response to the nonfibrogenic agents C5a, S. pneumoniae and aSiO(2) was brief or nonexistent, falling to baseline values within 3 d, whereas that to the fibrogenic agents bleomycin and mu XSiO2 persisted for up to 4 wk. Neutrophil numbers in the lung were proportional to the (18)FDG signal following C5a and S. pneumoniae, but not bleomycin and mu XSiO2. Autoradiography of lungs following administration of (H-3)-deoxyglucose [(H-3)-DC] showed specific localization to neutrophils in all models. Thus,(18)FDG 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.