Mehrad Borna, Burdick Marie D, Wandersee Nancy J, Shahir Kaushik S, Zhang Liyun, Simpson Pippa M, Strieter Robert M, Field Joshua J
Division of Pulmonary & Critical Care Medicine, Department of Medicine, and Beirne B. Carter Center for Immunology, University of Virginia, Charlottesville, VA.
Medical Sciences Institute and Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, WI; and.
Blood Adv. 2017 Nov 6;1(24):2217-2224. doi: 10.1182/bloodadvances.2017010777. eCollection 2017 Nov 14.
Lung injury and fibrosis are common in patients with sickle cell disease (SCD). Fibrocytes, a population of circulating, bone marrow-derived cells, have been linked to development and progression of tissue fibrogenesis and have been implicated in the development of lung fibrosis in preclinical models of SCD. We tested the hypothesis that the levels and activation state of circulating fibrocytes during steady state are associated with abnormal pulmonary function in adults with SCD. In a prospective cohort of steady-state adults with SCD and healthy age- and race-matched control participants, we measured the concentration and activation state of circulating fibrocytes and assessed pulmonary phenotype with pulmonary function tests (PFTs), a respiratory questionnaire, 6-minute walk test, high-resolution chest computed tomography scan, and echocardiogram. Seventy-one adults with SCD and 26 healthy African American control participants were examined. Compared with control participants, patients with SCD demonstrated higher levels of circulating fibrocytes, a significant proportion of which expressed the activation marker α-smooth muscle actin. Within patients with SCD, elevated absolute concentrations of circulating fibrocytes were strongly and independently associated with impaired lung physiology, as measured by PFTs. We conclude that elevated circulating fibrocytes are associated with lung disease in adults with SCD during steady state, consistent with a role for these cells in pathogenesis of lung fibrosis in this disease. Circulating fibrocytes may represent a novel biomarker for progressive pulmonary fibrosis in patients with SCD.
肺损伤和肺纤维化在镰状细胞病（SCD）患者中很常见。纤维细胞是一类循环的、源自骨髓的细胞，与组织纤维生成的发展和进程有关，并且在SCD的临床前模型中与肺纤维化的发展有关。我们检验了这样一个假设：在稳态期间循环纤维细胞的水平和激活状态与成年SCD患者的肺功能异常有关。在一个由成年稳态SCD患者以及年龄和种族匹配的健康对照参与者组成的前瞻性队列中，我们测量了循环纤维细胞的浓度和激活状态，并通过肺功能测试（PFT）、一份呼吸问卷、6分钟步行试验、高分辨率胸部计算机断层扫描和超声心动图评估了肺表型。对71名成年SCD患者和26名健康非裔美国对照参与者进行了检查。与对照参与者相比，SCD患者表现出循环纤维细胞水平更高，其中很大一部分表达激活标志物α-平滑肌肌动蛋白。在SCD患者中，通过PFT测量，循环纤维细胞的绝对浓度升高与肺生理功能受损密切且独立相关。我们得出结论，在稳态期间，循环纤维细胞升高与成年SCD患者的肺部疾病有关，这与这些细胞在该疾病肺纤维化发病机制中的作用一致。循环纤维细胞可能代表SCD患者进行性肺纤维化的一种新型生物标志物。
