Yoshino T, Tamura M, Kawabe M, Nomura H, Imai N, Ono M
Fujigotemba Research Laboratories, Chugai Pharmaceutical Co. Ltd, Shizuoka, Japan.
Br J Haematol. 1992 Dec;82(4):664-70. doi: 10.1111/j.1365-2141.1992.tb06941.x.
We have studied the effects of recombinant human granulocyte colony-stimulating factor (rG-CSF) on granulopoiesis and neutrophil functions in aged rats and aged mice. We subcutaneously injected rG-CSF or control vehicle into aged rats (22 months old and 25 months old) for 7 consecutive days, counted the peripheral neutrophils and evaluated the functions of neutrophils isolated from venous blood. The peripheral neutrophil count in aged rats tended to be increased as compared with that in young rats (11 weeks old). However, the neutrophils in aged rats exhibited a decline of superoxide anion (O2-) release and phagocytic activity as compared with young rats. The peripheral neutrophil count in aged rats was significantly increased 5-6-fold as many as the control value by rG-CSF treatment, which was accompanied by a significant enhancement of O2- release and of phagocytic activity being restored to normal levels or better. In another series of experiments, we subcutaneously injected rG-CSF or control vehicle into aged mice (24-28 months old) or young mice (8 weeks old) for 7 consecutive days, and evaluated the functions of neutrophils isolated from peritoneal cavity. The peritoneal exudate neutrophils from the aged mice exhibited a decline of phagocytic and chemotactic activity as compared with the young mice. These functions in both young and aged mice were significantly enhanced by rG-CSF-treatment, and these functions in rG-CSF-treated aged mice were restored to a level higher than the level in control young mice. These findings demonstrate that rG-CSF is capable of enhancing granulopoiesis and restoring the age-related decline of neutrophil functions.
我们研究了重组人粒细胞集落刺激因子(rG-CSF)对老年大鼠和老年小鼠粒细胞生成及中性粒细胞功能的影响。我们连续7天皮下注射rG-CSF或对照载体到老鼠(22月龄和25月龄)体内,计数外周血中性粒细胞,并评估从静脉血中分离出的中性粒细胞的功能。与年轻大鼠(11周龄)相比,老年大鼠外周血中性粒细胞计数有增加的趋势。然而,与年轻大鼠相比,老年大鼠的中性粒细胞超氧阴离子(O2-)释放和吞噬活性下降。rG-CSF治疗使老年大鼠外周血中性粒细胞计数显著增加至对照值的5-6倍,同时O2-释放显著增强,吞噬活性恢复到正常水平或更好。在另一系列实验中,我们连续7天皮下注射rG-CSF或对照载体到老年小鼠(24-28月龄)或年轻小鼠(8周龄)体内,并评估从腹腔分离出的中性粒细胞的功能。与年轻小鼠相比,老年小鼠腹腔渗出液中性粒细胞的吞噬和趋化活性下降。rG-CSF治疗显著增强了年轻和老年小鼠的这些功能,且rG-CSF治疗的老年小鼠的这些功能恢复到高于对照年轻小鼠的水平。这些发现表明,rG-CSF能够增强粒细胞生成并恢复与年龄相关的中性粒细胞功能衰退。