Department of Anesthesiology and Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Key Laboratory of Transplant Engineering and Immunology of the Health Ministry of China, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Interact Cardiovasc Thorac Surg. 2020 Aug 1;31(2):210-220. doi: 10.1093/icvts/ivaa074.
Progenitor cells mobilized by granulocyte colony-stimulating factor (G-CSF) have been shown to lessen acute kidney injury induced by extracorporeal circulation (ECC). Both acute kidney injury and lung injury are characterized by endothelial dysfunction. Our goal was to examine whether and how G-CSF-mobilized progenitors with endothelial capacity may help mitigate ECC-induced pulmonary dysfunction.
G-CSF (10 μg/kg/day) was administered subcutaneously to C57BL/6 mice before or at the initiation of the ECC process, after which lung injury was assessed by measuring neutrophils in the fluid from bronchoalveolar lavage and determining the pathological score in lung tissue. CD133+ progenitors were isolated and injected into C57BL/6 mice before ECC in vivo. We incubated the CD133+ cells with pulmonary monocytes or neutrophils isolated from naïve mice in vitro.
Pretreatment with G-CSF for 2 days significantly decreased the number of neutrophils in the bronchoalveolar lavage fluid, and the pathological score (P < 0.01; n = 5) improved the PaO2/FiO2 ratio [193.4 ± 12.7 (ECC without G-CSF) vs 305.6 ± 22.6 mmHg (ECC with G-CSF); P = 0.03, n = 5] and suppressed neutrophil elastase and tumour necrosis factor-α levels in the circulation; we also observed increases in both circulating and pulmonary populations of CD133+ progenitors. Similar effects were observed in animals pretreated with CD133+ progenitors instead of G-CSF before ECC. The majority of CD133+/CD45- and CD133+/CD45+ progenitors were mobilized in the lung and in the circulation, respectively. Incubating CD133+ progenitors with neutrophils or pulmonary monocytes blocked lipopolysaccharide-induced release of inflammatory factors.
Our results suggest that pretreatment of G-CSF attenuates ECC-induced pulmonary dysfunction through inhibiting the inflammatory response in lung tissue and in the circulation with associated premobilization of CD133+ progenitors.
粒细胞集落刺激因子（G-CSF）动员的祖细胞已被证明可以减轻体外循环（ECC）引起的急性肾损伤。急性肾损伤和肺损伤的特征均为内皮功能障碍。我们的目标是研究 G-CSF 动员的具有内皮能力的祖细胞是否以及如何帮助减轻 ECC 引起的肺功能障碍。
在 ECC 过程之前或开始时，向 C57BL/6 小鼠皮下给予 G-CSF（10μg/kg/天），然后通过测量支气管肺泡灌洗液中的中性粒细胞并确定肺组织中的病理评分来评估肺损伤。CD133+祖细胞在体内 ECC 之前被分离并注入 C57BL/6 小鼠。我们将 CD133+细胞与从幼稚小鼠分离的肺单核细胞或中性粒细胞在体外孵育。
预处理 2 天的 G-CSF 可显著减少支气管肺泡灌洗液中的中性粒细胞数量，病理评分（P<0.01；n=5）改善 PaO2/FiO2 比值[193.4±12.7（无 G-CSF 的 ECC）比 305.6±22.6mmHg（ECC 与 G-CSF）；P=0.03，n=5]，并抑制循环中的中性粒细胞弹性蛋白酶和肿瘤坏死因子-α水平；我们还观察到循环和肺内 CD133+祖细胞的数量均增加。在 ECC 前用 CD133+祖细胞代替 G-CSF 预处理的动物中也观察到类似的效果。大多数 CD133+/CD45-和 CD133+/CD45+祖细胞分别在肺和循环中动员。将 CD133+祖细胞与中性粒细胞或肺单核细胞孵育可阻止脂多糖诱导的炎症因子释放。
我们的结果表明，G-CSF 预处理通过抑制肺组织和循环中的炎症反应，以及与 CD133+祖细胞的预先动员，减轻 ECC 引起的肺功能障碍。
