Granulocyte-macrophage colony-stimulating factor （GM-CSF） and T-cell responses： what we do and don＇t know

Granulocyte-macrophage colony-stimulating factor （GM-CSF） is an important hematopoietic growth factor and immune modulator. GM-CSF also has profound effects on the functional activities of various circulating leukocytes. It is produced by a variety of cell types including T cells, macrophages, endothelial cells and fibroblasts upon receiving immune stimuli. Although GM-CSF is produced locally, it can act in a paracrine fashion to recruit circulating neutrophils, monocytes and lymphocytes to enhance their functions in host defense. Recent intensive investigations are centered on the application of GM-CSF as an immune adjuvant for its ability to increase dendritic cell （DC） maturation and function as well as macrophage activity. It is used clinically to treat neutropenia in cancer patients undergoing chemotherapy, in AIDS patients during therapy, and in patients after bone marrow transplantation. Interestingly, the hematopoietic system of GM-CSF-deficient mice appears to be normal; the most significant changes are in some specific T cell responses. Although molecular cloning of GM-CSF was carried out using cDNA library oft cells and it is well known that the T cells produce GM-CSF after activation, there is a lack of systematic investigation of this cytokine in production by T cells and its effect on T cell function. In this article, we will focus mainly on the immunobiology of GM-CSF in T cells.

Granulocyte-macrophage colony-stimulating factor protects mice against hepatocellular carcinoma by ameliorating intestinal dysbiosis and attenuating inflammation

BACKGROUND Hepatocellular carcinoma(HCC)is the third leading cause of cancer mortality worldwide.The gut microbiota can help maintain healthy metabolism and immunity.Granulocyte-macrophage colony-stimulating factor(GM-CSF)is a critical factor in promoting health and homeostasis;it promotes intestinal immunity,stimulates bone marrow precursors to generate macrophage colonies,and enhances the antibacterial and antitumor activity of circulating monocytes.As such,GM-CSF may protect against HCC development by regulating immunity as well as intestinal microecology.AIM To investigate the impact of GM-CSF on the gut microbiome and metabolic characteristics of HCC.METHODS Thirty-six male BALB/c nude mice were divided into three groups:Control(n=10),HCC(n=13),and HCC+GM-CSF(GM-CSF overexpression,n=13).We utilized HCC cells to establish orthotopic transplantation tumor models of HCC with normal and over-expressing GM-CSF.Liver injury,immune inflammatory function and intestinal barrier function were evaluated.The fecal microbiome and metabolome were studied using 16S rRNA absolute quantification sequencing and gas chromatography-mass spectrometry.RESULTS GM-CSF overexpression significantly affected the gut microbiome of mice with HCC and resulted in a high abundance of organisms of the genera Roseburia,Blautia and Butyricimonass,along with a significant reduction in Prevotella,Parabacteroides,Anaerotruncus,Streptococcus,Clostridium,and Mucispirillum.Likewise,GM-CSF overexpression resulted in a substantial increase in fecal biotin and oleic acid levels,along with a prominent decrease in the fecal succinic acid,adenosine,fumaric acid,lipoic acid,and maleic acid levels.Correlation analysis revealed that the intestinal microbiota and fecal metabolites induced by GM-CSF were primarily involved in pathways related to reducing the inflammatory response,biotin metabolism,and intestinal barrier dysfunction.CONCLUSION GM-CSF can protect against HCC development by regulating immunity and modulating the abundance of specific intestinal microorganisms and their metabolites.This study provides new insights into the therapeutic approaches for HCC.

Granulocyte-macrophage colony stimulating factor improves cardiac function in rabbits following myocardial infarction

Objective: To investigate the therapeutic potency of recombinant human Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) in a rabbit myocardial infarction model. Methods: A myocardial infarction was created by the ligation of the major ventricular branch of the left coronary artery in rabbits. After myocardial infarction, the animals were randomly assigned to GM-CSF treatment group, untreated groups and sham-operated group. The rabbits of the treated group were injected into GM-CSF by subcutaneous administration, 10 μg/kg/day, once a day for 5 days. The untreated and sham-operated group received a equal saline in the same manner as treated group. Six weeks later echocardiography and haemodynamic assessment were undertaken to assesse cardiac function. The size of the infarct region of the heart were also studied. Results: The untreated group exhibited significant higher left ventricle end-diastolic pressure, higher central venous pressure, and with significant lower mean blood pressure, lower peak first derivative of left ventricle pressure (dP/dt) than the sham group. Also, Rabbits in untreated group display significant systolic dysfunction shown by the decreased ejection fraction, diastolic dysfunction shown by increasing in the ratio of E wave to A wave (E/A), and display left ventricle enlargement. However, GS-CSF singnificantly prevented heart dysfunction, left ventricle enlargement, and reduced infarct size in treatment group. Conclusion: Administration GM-CSF after cardiac infarction can improve heart function. These findings indicate the technique may be a novel and simple therapeutic method for ischemic myocardium.

Granulocyte-macrophage colony-stimulating factor-transfected bone marrow stromal cells for the treatment of ischemic stroke

Adult, male, Sprague-Dawley rats were injected with granulocyte-macrophage colony-stimulating factor-transfected bone marrow stromal cells （GM-CSF-BMSCs） into the ischemic boundary zone at 24 hours after onset of middle cerebral artery occlusion. Results showed reduced infarct volume, decreased number of apoptotic cells, improved neurological functions, increased angiogenic factor expression, and increased vascular density in the ischemic boundary zone in rats that underwent GM-CSF-BMSCs transplantation compared with the BMSCs group. Experimental findings suggested that GM-CSF-BMSCs could serve as a potential therapeutic strategy for ischemic stroke and are superior to BMSCs alone.

CONSTRUCTION OF EUKARYOTIC EXPRESSION VECTOR WITH GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR GENE

Objective: To construct the eukaryotic expression vector that express human granulocyte-macrophage colony-stimulating factor (hGM-CSF) gene for making highly express in mammalian cells. Methods: Extract totally RNA from the induced human fetal lung (HFL) cell line. HGM-CSF cDNA was obtained by reverse transcription-polymerase chain reaction (RT-PCR), and then directionally subcloned into the HindIII and EcoRI site on the pcDNA3.1 plasmid, which was controlled by the CMV promoter, to form the recombinant expressing vector pcDNA3.1-GM-CSF. Results: The PCR amplification was identified and the sequence was analyzed, the results showed that hGM-CSF was properly inserted into the vector and the sequence was correct.

ANTITUMOR EFFECT OF GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR(GM-CSF)-GENE ENCODED VACCINIA MELANOMA ONCOLYSATE AND ITS IMMUNOLOGICAL MECHANISMS

Vaccinia melanoma oncolysate (VMO) prepared by infecting B16F10 melanoma cells with recombinant vaccinia virus encoding murine GMCSF gene was tested for its therapeutic effect on the preestablished melanoma. C57BL/6 mice were inoculated s.c. with 1×105 B16F10 melanoma cells and received s.c. administration with VMO prepared with GMCSF gene encoded vaccinia virus(GMCSFVMO), VMO prepared with thymidine kinase genedeficient vaccinia virus(TKVMO), B16F10 melanoma oncolysate(BMO), or PBS 3 days after tumor inoculation. The same treatment was bolstered one week later. The results demonstrated that GMCSFVMO treatment significantly inhibited the growth of subcutaneous tumor and prolonged the survival period of tumorbearing mice. Further study elucidated that cytotoxicity of PBL and splenocytes towards B16F10 increased obviously after treatment with GMCSFVMO, but NK activity remained unchanged. These results suggest that the tumor oncolysate vaccine prepared with GMCSF geneencoded vaccinia virus might exert potent therapeutic effect on the preestablished tumor through the efficient induction of specific antitumor immune response of the host.

EFFECTS OF GRANULOCYTE-MACROPHAGE COLONY STIMULATING FACTOR GENE ENCODED VACCINIA VIRUS VECTOR ON MURINE PULMONARY METASTATIC MELANOMA

A recombinant vaccinia virus expressing murine granulocyte-macrophage colony-stimulating factor (VVGM-CSF) was tested for its antitumor activity.Murine pulmonary metastasis was established by injecting 20×10~5 B16F10 melanoma cells into the tail vein of C57BL/6 mice. Three days after B16F10 inoculation,WGM-CSF or VVTK, a thymidine kinase gene deficient control vaccinia virus, were injected intraperitoneally twice weekly for 2 weeks. Two weeks later, the mice were sacrificed and pulmonary metastasis fool counted.The results demonstrated that VVGM-CSF treatment significantly decreased the number of pulmonary metastasis and prolonged the survival time of tumorbearing mice. Cytotoxic and phagocytic activities of the peritoncal macrophages were found to be markedly elevated in mice treated with WGM-CSF. Nitric oxide released from the macrophages was also found to be increased. These data, together with our other results,strongly demonstrated that continuous secretion of GMCSF and activation of macrophages might pal-tially explain the therapeutic effects of VVGM-CSF on murine pulmonary metastasis.

Application of pegylated recombinant human granulocyte colony-stimulating factor(PEG-rhG-CSF) for the prevention of neutropenia in triple negative breast cancer patients older than 65 years during adjuvant chemotherapy

Objective The aim of this study was to compare the efficacy and safety of pegylated recombinant human granulocyte colony-stimulating factor(PEG-rhG-CSF)and recombinant human granulocyte colonystimulating factor(rhG-CSF)for the prevention of neutropenia in elderly breast cancer patients during adjuvant chemotherapy.Methods A total of 45 oncology inpatients with breast cancer,who received adjuvant chemotherapy and were older than 65 years from May 2017 to October 2018 in the General Hospital of the Northern Theater of the Chinese people’s Liberation Army,were included.Epirubivin Cyclophoshamide-Docetaxel(EC-T)sequential adjuvant chemotherapy was chosen.Forty-five patients were randomly divided into two groups;25 patients in the treatment group were treated with PEG-rhG-CSF and 20 patients in the control group were not treated with PEG-rhG-CSF,but only rhG-CSF.The experimental group was treated with the PEG-rhG-CSF at the end of chemotherapy for 24–48 h,with a 6 mg subcutaneous injection once per chemotherapy cycle.In the control group,rhG-CSF was administered after 48 h of chemotherapy,with a 100μg subcutaneous injection,1/d,d 1–7.The dosage could be increased step by step with the exacerbation of neutropenia.The primary aims of this study was to discover the incidence of leukopenia,neutropenia,neutrophilic fever,and adverse reactions in the two groups.Results The incidence of neutropenia,neutrophilic fever and adverse reactions decreased in the treatment group compared to the control group,but no significant difference existed between two groups(P>0.05).Patients in treatment group had a lower,but not statistically significant,incidence of adverse reactions(P>0.05).Conclusion Applying PEG-rhG-CSF could be effective in preventing neutropenia in elderly patients with postoperative adjuvant chemotherapy to treat breast cancer.It may effectively control the occurrence of neutropenia after chemotherapy and reduce the chance of infection.The incidence of side effects,such as fever and bone pain,was low.The adverse drug reactions were well tolerated by patients,which could ensure the smooth progress of chemotherapy.

Mudskipper interleukin-34 modulates the functions of monocytes/macrophages via the colony-stimulating factor-1 receptor 1

Interleukin-34(IL-34)is a novel cytokine that plays an important role in innate immunity and inflammatory processes by binding to the colonystimulating factor-1 receptor(CSF-1R).However,information on the function of IL-34 in fish remains limited.In the present study,we identified an IL-34 homolog from mudskippers(Boleophthalmus pectinirostris).In silico analysis showed that the mudskipper IL-34(BpIL-34)was similar to other known IL-34 variants in sequence and structure and was most closely related to an orange-spotted grouper(Epinephelus coioides)homolog.BpIL-34 transcripts were constitutively expressed in various tissues,with the highest level of expression found in the brain.Edwardsiella tarda infection significantly up-regulated the mRNA expression of BpIL-34 in the mudskipper tissues.The recombinant mature BpIL-34 peptide(rBpIL-34)was purified and used to produce anti-rBpIL-34 IgG.Western blot analysis combined with PNGase F digestion revealed that native BpIL-34 in monocytes/macrophages(MOs/MФs)was N-glycosylated.In vitro,rBpIL-34 treatment enhanced the phagocytotic and bactericidal activity of mudskipper MOs/MФs,as well as the mRNA expression of pro-inflammatory cytokines like tumor necrosis factorα(BpTNF-α)and BpIL-1βin these cells.Furthermore,the knockdown of mudskipper CSF-1R1(BpCSF-1R1),but not mudskipper BpCSF-1R2,significantly inhibited the rBpIL-34-mediated enhanced effect on MO/MФfunction.In conclusion,our results indicate that mudskipper BpIL-34 modulates the functions of MOs/MФs via BpCSF-1R1.

Granulocyte-macrophage colony-stimulating factor and interleukin 4 induce the malignant transformation of the bone marrow- derived human adult mesenchymal stem cells

Background The purpose of the study was to examine the effects of granulocyte-macrophage colony-stimulating factor （GM-CSF） and interleukin 4 （IL-4） on the bone-marrow-derived human adult mesenchymal stem cells （hMSCs）. Methods The hMSCs were isolated and cultured with GM-CSF and IL-4 for a period of one month. A single colony of transformed cells was then isoloated and their phenotype was characterized by morphology, surface marker expression, and in vivo tumorigenesis.Results After one month culture, the transformed mesenchymal cells exhibited the morphology and phenotype similar to those of tumor cells, and also caused multiple fast growing lung deposits when it was injected into immunodeficient mice.Conclusion Cytokines-driven malignant transformation of hMSCs may be a useful model for studying signaling pathways initiating malignant transformation of hMSC.

Effects of granulocyte-macrophage colony stimulating factor on the repair of vessel intima damaged by balloon

The dysfunction of vascular endothelial cells plays a key role in startingand facilitating restenosis. The acceleration of intima repair and the recovery of endothelialfunction would reduce the restenosis rate. This study was undertaken to assess the effect ofgranulocyte-macrophage colony stimulating factor ( GM-CSF) on the repair of damaged iliac arteries.Twenty-four male New Zealand white rabbits undergoing primary iliac artery deendothelialization wererandomly divided into two groups ( GM-CSF group and control group) . The GM-CSF group received asubcutaneous injection of GM-CSF (10 μg ? kg^(-1) ? d^(-1) ) , and the control groupwas given a subcutaneous injection of equivalent saline. The iliac arteries of all animals weredamaged by balloon after 7 days. The levels of nitric oxide ( NO) were detected before, 1 week, 2weeks and 4 weeks after angioplasty. The repair and hyperplasia of the intima were observedmicroscopically and the indices of stenosis were evaluated by computerized planimetry after 4 weeksof angioplasty. The NO levels of the GM-CSF group were higher than those of the control group 2weeks and 4 weeks after angioplasty [91.92 +-11.57) μmol/L vs. (81. 67 +- 12. 18) μmol/L; (97. 67+- 10. 13 ) ( μmol/L vs. (83. 16 +-12. 64) μmol/L]. Four weeks after balloon damage,histological examination showed that neointima formation, vascular smooth muscle cells and fibroustissue of the GM-CSF group were less than those of the control group. The endothelium of the GM-CSFgroup was more integrated, and stenosis of lumen was slighter than that of the control group.Morphometry showed the lumen area of the GM-CSF group was larger than that of the control group[(1.27 +-0. 31) mm^2 vs. (0. 92 +- 0. 24) mm^2 ] , the neointimal area and percent of intimahyperplasia were significantly smaller than those of the control group [ (0. 85 +-0. 34) mm vs. (1.18 +-0. 38) mm^2; (40 +- 7)% vs. (55 +- 6)%]. GM-CSF could facilitate the repair of the intima,reduce neointima formation, better the function of the endothelium, and decrease the rate ofrestenosis.

实体瘤自体造血干细胞动员不佳患儿应用普乐沙福的经验分享

目的 分析普乐沙福对实体瘤自体造血干细胞动员不佳患儿的作用及安全性。方法 回顾性分析5例实体瘤造血干细胞动员不佳患儿的临床资料,所有患儿均应用普乐沙福自体造血干细胞动员,分析干细胞动员血象变化、采集结果及不良反应发生情况。结果 外周血(PB) CD34^(+)细胞计数<10 cells/μl及第1天采集物CD34^(+)细胞计数<1.5×10^(6)/kg时及时加用普乐沙福;加用普乐沙福后1例采集1次,1例采集2次,3例采集3次。5例患儿中3例采集成功。未出现乏力、失眠、腹痛、腹泻、头晕、关节痛等不良反应。3例患儿已行自体干细胞移植,粒细胞及血小板均植入。结论 外周血CD34^(+)细胞计数<10 cells/μl及第1天采集物CD34^(+)细胞计数<1.5×10^(6)/kg时加用普乐沙福获得采集成功普乐沙福用于实体瘤动员不佳患儿自体造血干细胞动员,不良反应少,耐受性好。

Clinical Study of Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor on Chemotherapy-Induced Leukopenia.

We have studied the efficacy and safery of recombinant human granulocyte-macrophate colony-stimulating factor

Serum profiles of circulating granulocyte-macrophage colony-stimulating factor in acute myocardial infarction and relation with post-infarction left ventricular function

Accumulating evidence indicates that inflammation plays an important role in cardiac repairing and remodeling after acute myocardial infarction （AMI）, process of which is mediated by a cytokine reaction cascade. 1 Granulocytemacrophage colony-stimulating factor （GM-CSF） is a cytokine, which belongs to the family of haemopoietic cell colony-stimulating factor and regulates the proliferation and differentiation of myeloid progenitor cells. In addition to its growthpromoting effects, this pro-inflammation cytokine stimulates the function of mature neutrophils, monocytes and eosinophils, including regulation of leukocyte adhesion, augmentation of surface antigen expression, superoxide anion generation, enhancement or induction of other cytokine production.

聚乙二醇化重组人粒细胞刺激因子预防化疗后中性粒细胞减少症的多中心上市后临床研究

目的:探究聚乙二醇化重组人粒细胞刺激因子(pegylated recombinant human granulocyte-colony stimulating factor,PEG-rhG-CSF)在多个化疗周期中预防中性粒细胞减少症的有效性和安全性。方法:本研究为多中心、前瞻性、开放性单臂临床试验,对需接受多周期化疗的肺癌、卵巢癌、结直肠癌等恶性实体瘤患者连续2~4个周期预防性给予PEG-rhG-CSF。结果:PEG-rhG-CSF初级预防给药后,4级中性粒细胞减少症的发生率从第1个化疗周期的4.76%(13/273)分别降至2~4个周期的1.83%(5/273)、1.15%(2/174)和2.08%(2/96),3级中性粒细胞减少症的发生率从第1个化疗周期的11.36%(31/273)分别降至2~4个周期的6.23%(17/273)、2.87%(5/174)和3.13%(3/96)。第1次随访发热性中性粒细胞减少症(febrile neutropenia,FN)的发生率为0.73%(2/273);FN持续时间中1例为2 d,1例为5 d;第2~4次随访的FN发生率均为0;次级预防给药后,4级中性粒细胞减少症的发生率从筛选期的25%(7/28),分别降至后续1~3个周期的3.57%(1/28)、0(0/28)和6.67%(1/15),3级中性粒细胞减少症的发生率则从71.43%(20/28)分别降至10.71%(3/28)、14.29%(4/28)和0(0/15)。研究中抗生素的使用率为10.48%(44/420)。结论:每个化疗周期应用1次PEG-rhG-CSF可有效预防恶性实体瘤患者化疗后中性粒细胞减少症的发生,多个周期应用可以显示同样的疗效,且安全性良好。

TNF-α在慢性根尖周炎骨破坏中的机制探讨

目的探讨牙髓卟啉单胞菌（Porphyromonas endodontalis,P.e）脂多糖（lipopolysaccharide,LPS）是否诱导成骨细胞产生肿瘤坏死因子α（tumor necrosis factor-α,TNF-α）及TNF-α是否通过核因子κB（nuclear factor-κB,NF-κB）信号通路上调巨噬细胞集落刺激因子（macrophage colony stimulating factor,M-CSF）的产生。方法以不同浓度P.e-LPS （0~50 mg/L）刺激MC3T3-El细胞和以10 mg/L P.e-LPS作用细胞不同时间（0~24 h）后,采用反转录-聚合酶链式反应（RT-PCR）检测TNF-α mRNA的表达;以不同浓度TNF-α（0~10 ng/L） 刺激MC3T3-El细胞后,采用RT-PCR和酶联免疫吸附试验（ELISA）检测M-CSF mRNA和蛋白的表达;再以ELISA方法检测BAY 11-7082对TNF-α 刺激MC3T3-El细胞后M-CSF蛋白表达的影响。采用SPSS 13.0软件包对结果进行单因素方差分析和Dunnett t检验。结果不同质量浓度的P.e-LPS（0~50 mg/L）刺激MC3T3-El细胞后,TNF-α mRNA的表达具有剂量依赖性;10 mg/L P.e-LPS作用MC3T3-El细胞6 h时,TNF-α mRNA 的表达量最大。随着作用时间的延长,TNF-α mRNA 的表达量逐渐下降;不同质量浓度TNF-α（0~10 ng/L）刺激MC3T3-El细胞后,M-CSF mRNA 和蛋白的表达具有剂量依赖性,蛋白表达量从（37±2） ng/L（空白对照组）增加到（301±8） ng/L（10 ng/L组）;10 mol/L BAY 11-7082预处理1 h可以降低TNF-α诱导成骨细胞M-CSF蛋白的表达水平,蛋白表达量从（253±14） ng/L（TNF-α组）下降到（154±2）ng/L（BAY＋TNF-α组）,而单独使用BAY 11-7082组与空白对照组相比差异无显著性。结论P.e-LPS诱导成骨细胞产生TNF-α,而TNF-α 上调M-CSF可能通过NF-κB信号通路,这意味着TNF-α可能在P.e-LPS致慢性根尖周炎骨破坏中对成骨细胞发挥自分泌作用。

粒细胞集落刺激因子与子宫内膜修复的研究进展

薄型子宫内膜(thin endometrium)在人类辅助生殖技术中越来越受到人们的重视。薄型内膜是指子宫内膜厚度不足以能够获得妊娠,即低于胚胎着床的阈厚度。子宫内膜的修复机制涉及女性体内多方面因素,除众所周知的下丘脑-腺垂体-卵巢轴的协同作用之外,细胞因子也在这一过程中通过自分泌或旁分泌起到关键作用,集落刺激因子(CSFs)就是其中之一。近年来的研究发现粒细胞集落刺激因子(G-CSFs)在子宫内膜增殖过程中起着一定程度上的正向促进作用。

rHuG-CSF动员健康供者外周血造血干细胞的效果观察

目的：观察重组人粒细胞集落刺激因子（recombinant human granulocyte-colony stimulating factor，rHuG．CSF）动员健康供者外周血造血干细胞的效果及影响因素。方法：将本研究中心异基因造血干细胞移植健康供者163例，分别采用3种不同厂家生产的rHuG-CSF进行外周血造血干细胞动员，对其动员效果、受者移植后造血重建等情况进行比较。结果：不同种rHuG-CSF动员后采集的单个核细胞（MNC）及CD34^＋细胞均能满足临床造血干细胞移植的需要，130例人类白细胞抗原（human leucocyte antigens，HLA）配型相合的同胞受者移植后均获得顺利植入。动员的单个核细胞数及CD34^＋细胞数与性别无关，而CD34^＋细胞数在41-60岁年龄组中明显减少（P〈0．05）；对采集时机的分析显示：第5天采集的单个核细胞数及CD34^＋细胞数最高（P〈0．05），此后逐渐下降。结论：糖基化的及两个非糖基化的rHuG-CSF制剂均能有效地在异基因移植中作为外周血造血干细胞动员剂。

地西他滨+CAG与HAG治疗老年初治急性髓性白血病的对比研究

目的评价地西他滨+CAG方案及HAG方案治疗老年初治急性髓性白血病(AML)的疗效及不良反应。方法 45例老年初治AML分为地西他滨+CAG治疗组及HAG治疗组,23例病人予以地西他滨+CAG方案治疗,22例病人予以HAG治疗,地西他滨+CAG治疗组病人在第1疗程后间歇21 d左右进行第2个疗程;HAG治疗组病人在第1疗程后间歇14 d左右进行第2个疗程,评价并比较2组疗效及不良反应。结果地西他滨+CAG治疗组的完全缓解(CR)率为78.3%,总有效率为95.7%;HAG治疗组CR率为54.5%,总有效率达为77.3%,2组比较差异无统计学意义。2组血液系统不良反应比较差异无统计学意义。结论地西他滨+CAG方案CR率及有效率与HAG方案相当、没有更多的不良反应,化疗强度,敏感性更大,在老年初治AML病人中值得推荐应用。

rhG-CSF对骨髓采集物中记忆T细胞上黏附分子表达的调节作用

本研究主要探讨人重组粒细胞集落刺激因子(rhG-CSF)对骨髓采集物记忆T细胞上黏附分子表达的调节作用。采用流式细胞仪检测稳态骨髓(SS-BM)和rhG-CSF预激的骨髓(G-BM)中CD4+、CD8+T细胞百分比及其记忆细胞表面黏附分子CD49d、CD54、CD62L和CD11a的表达。结果显示:rhG-CSF应用后骨髓采集物中CD4+、CD8+T细胞在淋巴细胞中的比例明显降低(p<0.001),记忆T细胞的比例没有明显变化;CD49d在CD4+和CD8+T细胞的表达百分比显著下降(p<0.05),但在记忆T细胞的表达百分比没有明显的变化;CD54在CD4+及其记忆T淋巴细胞和CD8+T淋巴细胞的表达百分比明显降低(p<0.05),而在CD8+记忆T细胞的表达百分比没有明显变化;CD62L在CD4+、CD8+及其记忆T细胞的表达百分比显著下降(p<0.01);CD11a在CD4+及其记忆T细胞的表达百分比明显降低(p<0.05),而在CD8+及其记忆T细胞的表达百分比没有明显变化。结论:rhG-CSF部分下调骨髓中CD4+、CD8+以及相应的记忆T细胞上黏附分子表达。