早产患者血清粒细胞集落刺激因子的检测及其意义

目的探讨粒细胞集落刺激因子(G-CSF)与自发性早产的关系及其对预测早产的可能意义。方法采用ELISA-双抗体夹心法分别对28-34周、34-37周不同孕龄组早产妇女及正常妊娠妇女的血清G-CSF进行检测。结果孕28-34周早产妇女血清G-CSF水平较正常对照组妇女升高(P<0.05)。结论高水平的血清G-CSF与妊娠<34周发生的早产有关,检测妊娠妇女血清G-CSF水平对预测妊娠34周之前发生的早产有重要意义。     

粒细胞集落刺激因子治疗下肢缺血性疾病

目的探讨粒细胞集落刺激因子(rhG-CSF)对下肢缺血模型血管新生的影响。方法制作兔左下肢缺血模型,术后随机分为rhG-CSF治疗实验组(n=24)和对照组(n=24);应用流式细胞学技术、动脉造影、免疫组织化学染色检查,比较两组外周血CD34 细胞的含量、缺血下肢侧枝血管计数及肌肉毛细血管密度。结果治疗后3 d实验组CD34 含量(%)为(0.7150±0.0873)明显高于对照组(0.3983±0.0853),差异有统计学意义(P<0.01);实验组在第15、30天时侧枝血管计数(6.33±0.82、9.17±0.75)均高于对照组(3.33±0.52、4.17±0.75)(P<0.01);第40天实验组内收肌毛细血管密度平均为8.5/HP,明显高于对照组4.2/HP(P<0.01)。结论rhG-CSF可以增加兔缺血下肢的毛细血管数量,有促进血管新生的作用。     

Urinary bladder carcinoma producing granulocyte colony stimulating factor (G-CSF): A case report with immunohistochemistry

A rare case of urinary bladder carcinoma with granulocyte colony stimulating factor (G-CSF) production was reported. In an 83-year-old female, marked neutrophilia in the peripheral blood decreased from 132,500/mm³ to 3,300/mm³ after tumour resection. The tumour was a transitional cell carcinoma. The serum G-CSF level reduced from 238 pg/ml pre-operatively to normal (60 pg/ml) after the operation. Immunohistochemical investigation of the resected tumour with monoclonal antibody specific for G-CSF revealed positive staining in the carcinoma cells, confirming G-CSF secretion.     

负载异体抗原对低剂量粒细胞巨噬细胞集落刺激因子诱导的树突状细胞免疫学性状的影响

目的观察低剂量粒细胞巨噬细胞集落刺激因子(GM-CSF)诱生的未成熟树突状细胞(GM~(low)DC)对异体抗原的摄取能力,以及负载异体抗原后细胞表型和功能的改变。方法对处于增殖期的C_(57)BL/6小鼠单个核细胞(MNC)作氚标记亮氨酸(~3H-Leu)掺入处理,制备~3H-Leu标记的抗原上清液。将此抗原上清液分别与昆明小鼠GM~(low)DC和成熟树突状细胞(DC)孵育30、60、90 min,检测细胞每分钟放射性荧光闪烁计数(cpm)值；用流式细胞仪检测负载异体抗原前后GM~(low)DC表面I~A/I~E、CD80分子的表达情况。分离C_(57)BL/6小鼠的T淋巴细胞,根据加入的刺激因素分组并进行同种混合淋巴细胞反应(MLR)：对照组(不加刺激因素)、GM~(low)DC组、GM~(low)DC+异体抗原组、GM~(low)DC+异体抗原+细胞毒性T淋巴细胞相关抗原4Ig(CTLA-4Ig)组。检测各组细胞cpm值,计算刺激指数(SI)。结果加入异体抗原上清液后30、60、90 min,GM~(low)DC的cpm值均明显高于同时相点的成熟DC(P＜0．05或0．01)。负载异体抗原前,GM~(low)DC细胞表面I~A/I~E的表达率为(32±8)%,CD80的表达率为(25±10)%；负载后两者分别为(54±10)%、(71±18)%,均明显升高(P＜0．05或0．01)。MLR：GM~(low)DC+异体抗原组细胞cpm值明显高于对照组(P＜0．05),SI＞2．0；GM~(low)DC组以及GM~(low)DC+异体抗原+CTLA-4Ig组细胞cpm值与对照组比较,差异无统计学意义(P＞0．05),AI均＜2．0。结论GM~(low)DC具有较强的抗原摄取能力,负载抗原后,细胞在表型及功能上渐趋成熟。应用CTLA-4Ig可阻断其免疫应答效应,建立免疫耐受。     

Granulocyte Colony-stimulating Factor Supports Liver Regeneration in a Small-for-size Liver Remnant Mouse Model

Experimental partial hepatectomy of more than 80% of the liver weight bears an increased mortality in rodents, due to impaired hepatic regeneration in small-for-size liver remnants. Granulocyte colony-stimulating factor (G-CSF) promotes progenitor cell expansion and mobilization and also has immunomodulatory properties. The aim of this study was to determine the effect of systemically administered G-CSF on liver regeneration and animal survival in a small-for-size liver remnant mouse model. Mice were preconditioned daily for 5 days with subcutaneous injections of 5 μg G-CSF or aqua ad injectabile. Subsequently, 83% partial hepatectomy was performed by resecting the median, the left, the caudate, and the right inferior hepatic lobes in all animals. Daily sham or G-CSF injection was continued. Survival was significantly better in G-CSF-treated animals (P < 0.0001). At 36 and 48 h after microsurgical hepatic resection, markers of hepatic proliferation (Ki67, BrdU) were elevated in G-CSF-treated mice compared to sham injected control animals (P < 0.0001) and dry liver weight was increased (P < 0.05). G-CSF conditioning might prove to be useful in patients with small-for-size liver remnants after extended hepatic resections due to primary or secondary liver tumors or in the setting of split liver transplantation. Presented at the Forty-seventh Annual Meeting of The Society for Surgery of the Alimentary Tract, Los Angeles, CA, May 14–19, 2006 (poster presentation).     

Prospective Randomized Study Comparing the Efficacy of Bioequivalent Doses of glycosylated and nonglycosylated rG-CSF for Mobilizing Peripheral Blood Progenitor Cells

Thirty patients diagnosed with breast cancer were included in a prospective randomized study comparing the in vivo priming effect of bioequivalent doses of glycosylated (lenograstim) and nonglycosylated (filgrastim) rG-CSF administration. Analysis of the efficacy of equivalent biological doses of both rG-CSFs showed no significant differences either in the mobilization of the subpopulations of PBPC considered (CD34⁺, CD34⁺/38⁻, CD34⁺/DR⁻), the content of such CD34⁺ cell subsets in the leukapheresis product, or the cost of the mobilization and collection procedures between both recombinant molecules. These results suggest that priming with bioequivalent doses of the two commercially available forms of glycosylated or nonglycosylated rG-CSF has a similar in vivo effect on PBPC mobilization.     

玄胡索散通过下调粒细胞集落刺激因子抑制脾脏髓源抑制细胞分化发挥抗乳腺癌作用

目的:探讨玄胡索散抑制乳腺癌小鼠脾脏髓源抑制细胞(MDSC)分化的作用机制。方法:4～5周龄BALB/c雌性小鼠48只,其中6只为正常对照组,其他42只采用小鼠左侧第二对乳腺皮下脂肪垫接种4T1细胞构建乳腺癌荷瘤小鼠模型,分为粒细胞集落刺激因子(G-CSF)对照组、G-CSF敲减组、模型对照组、玄胡索散小剂量组、玄胡索散中剂量组、玄胡索散大剂量组和环磷酰胺组,每组6只。其中G-CSF对照组和G-CSF敲减组分别采用shRNA慢病毒转染联合嘌呤霉素构建相应4T1稳转细胞模型。各组造模48 h后,玄胡索散小剂量组、玄胡索散中剂量组、玄胡索散大剂量组分别按2、4、8 g·kg^-1·d^-1玄胡索散灌胃,每天一次;环磷酰胺组按30 mg/kg腹腔注射环磷酰胺,隔天一次;其他组给予等体积0.5%羟甲基纤维素纳。各组连续给药25 d。苏木精-伊红染色观察脾脏组织病理学改变,流式细胞术测定脾脏MDSC亚群比例,免疫荧光法检测脾脏CD11b、Ly6G共表达,酶联免疫吸附测定外周血G-CSF浓度。在体外,建立荷瘤小鼠脾脏与4T1稳转株共培养体系,玄胡索散(30μ...     

Adhesion dependent release of hepatocyte growth factor and interleukin-1 receptor antagonist from human blood granulocytes and monocytes: Evidence for the involvement of plasma IgG,complement C3 and β2 integrin

Objective:Evolving evidence of anti-inflammatory effects is observed in patients with rheumatoid arthritis or ulcerative colitis following periodic adsorptive granulocyte and monocyte (GM) apheresis with a column containing cellulose acetate (CA) beads as apheresis carriers. This study was undertaken to obtain insights into mechanisms of anti-inflammatory actions of adsorptive GM apheresis with CA beads. Methods:In a series of in-vitro experiments, we investigated the effects of plasma proteins and the leucocytes 2 integrin (CD18) on granulocyte adsorption to CA beads. Results:Granulocyte adsorption to CA beads required plasma IgG, the complement C3 and was inhibited by an antibody to leucocytes CD18. Further, hepatocyte growth factor (HGF) and interleukin-1 receptor antagonist (IL-1ra) which have strong anti-inflammatory actions were released by granulocytes that adhered to CA beads. Conclusions:Plasma IgG, C3 derived complement activation fragments and leucocytes CD18 are involved in granulocyte adhesion to CA beads and hence the release of HGF and IL-1ra.Received 27 October 2003; returned for revision 16 December 2003; accepted by M. J. Parnham 8 January 2004     

Granulocyte colony-stimulating factor treatment in AIDS patients

Summary Frequent complications of human immunodeficiency virus infection are hematopoietic failure and poor tolerance of myelosuppressive drugs. Reasons for neutropenia resulting from hematopoietic failure are infection of the bone marrow and hematotoxicity of treatment with zidovudine, ganciclovir, sulfonamides, and interferons. Moreover, tumor necrosis factor-, transforming growth factor- and interferon- have been shown to suppress proliferation of bone marrow cells. Both granulocyte (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) increase neutrophil counts and ameliorate phagocytic and bactericidic function of neutrophils. We report eight cases of AIDS patients with serious infections and neutropenia (< 750 cells/l), who were treated concomitantly with recombinant human G-CSF (3–4 g subcutaneously per kilogram body weight daily). G-CSF treatment was well tolerated in all patients and showed no side effects or disturbances of other lineages than neutrophils. Life-threatening bacterial infections were treated successfully by stimulating the neutrophil immune system. This therapy shortened the duration of subsequent treatment with antibiotics. Since human immunodeficiency virus infects CD4-positive monocytes and macrophages, which are stimulated by GM-CSF, G-CSF seems to be the cytokine of choice, if stimulation of the neutrophil lineage is warranted.Abbreviations G-CSF granulocyte colony-stimulating factor - GM-CSF granulocyte-macrophage colony-stimulating factor - HIV human immunodeficiency virus     

The time course of leucocyte colony-formation in cultures of bone-marrow progenitor cells from rats and dogs

The colony-forming units granulocyte and macrophage (CFU-GM) assay, using either rat or dog haematopoietic progenitor cells, assesses the toxicity of new compounds. To identify the characteristics of colony formation in this system, a time-course study of CFU-GM assays using rat and dog bone marrow cells was tested. Neutrophil colonies, macrophage colonies and mixed colonies of neutrophils and macrophages were formed in soft agar medium. Neutrophil colonies reached their maximum number on days 3–4 and decreased markedly thereafter. Macrophage colonies reached their maximum number on days 7–8 and remained steady thereafter. Only a small number of mixed colonies of neutrophils and macrophages were formed beginning around day 4. There were no significant differences between rat and dog bone marrow cells in the occurrence of these maxima, or in any other growth phenomenon. This result suggests that to evaluate the influence of compounds on neutrophil colonies and macrophage colonies, observations should be made on days 4 and 8, respectively.