Carulli Giovanni, Mattii Letizia, Azzarà Antonio, Brizzi Stefania, Galimberti Sara, Zucca Alessandra, Benedetti Edoardo, Petrini Mario
Division of Hematology, Department of Oncology, Transplants and Advanced Technologies in Medicine, University of Pisa, Pisa, Italy.
Am J Hematol. 2006 May;81(5):318-23. doi: 10.1002/ajh.20604.
Neutrophil functions can be modified by Recombinant human G-CSF (rhG-CSF) treatment, with divergent effects on phagocytosis, motility, bactericidal activity, and surface molecule expression. Neutrophil morphology is modified by treatment with filgrastim (the nonglycosylated form of rhG-CSF), while it is not affected by lenograstim (the glycosylated type of rhG-CSF). Little information is available about actin polymerization in neutrophils from subjects treated with the two types of rhG-CSF. In the current paper we evaluated two groups of donors of peripheral blood stem cells (PBSC) for allogeneic transplantation. Ten subjects were treated with filgrastim and 10 with lenograstim to mobilize PBSC; 15 blood donors were evaluated as a control group. Actin polymerization (both spontaneous and fMLP-stimulated) was studied by a flow cytometric assay. A microscopic fluorescent assay was also carried out to evaluate F-actin distribution in neutrophils. We found that filgrastim induced an increased F-actin content in resting neutrophils, along with morphologic evidence for increased actin polymerization distributed principally at the cell membrane and frequently polarized in focal areas; in addition, fMLP was not able to induce further actin polymerization. On the contrary, treatment with lenograstim was associated with F-actin content, distribution, and polymerization kinetics indistinguishable from those displayed by control neutrophils. Such experimental results show that filgrastim and lenograstim display divergent effects also on neutrophil actin polymerization and provide further explanation for previous experimental findings.
重组人粒细胞集落刺激因子(rhG-CSF)治疗可改变中性粒细胞的功能,对吞噬作用、运动性、杀菌活性及表面分子表达产生不同影响。非格司亭(rhG-CSF的非糖基化形式)治疗可改变中性粒细胞形态,而培非格司亭(rhG-CSF的糖基化形式)则无此作用。关于接受这两种rhG-CSF治疗的受试者中性粒细胞中肌动蛋白聚合的信息较少。在本文中,我们评估了两组用于异基因移植的外周血干细胞(PBSC)供体。10名受试者接受非格司亭治疗,10名接受培非格司亭治疗以动员PBSC;15名献血者作为对照组进行评估。通过流式细胞术检测研究肌动蛋白聚合(自发和fMLP刺激)情况。还进行了显微镜荧光检测以评估中性粒细胞中F-肌动蛋白的分布。我们发现,非格司亭可使静息中性粒细胞中的F-肌动蛋白含量增加,同时有形态学证据表明肌动蛋白聚合增加,主要分布在细胞膜,且常在局部区域极化;此外,fMLP无法诱导进一步的肌动蛋白聚合。相反,培非格司亭治疗与F-肌动蛋白含量、分布及聚合动力学与对照中性粒细胞无差异。这些实验结果表明,非格司亭和培非格司亭对中性粒细胞肌动蛋白聚合也有不同影响,并为先前的实验结果提供了进一步解释。