Granulocyte chemiluminescence response to serum opsonized zymosan particlesex vivo during long-term strenuous exercise,energy and sleep deprivation in humans

The chemiluminescence response of granulocytes to serum opsonized zymosan particles (SOZ) ex vivo was investigated during two ranger training courses lasting 7 days with continuous moderate physical activities corresponding to about 32% of maximal oxygen uptake or 35 000 kJ · 24 h⁻¹, with energy deficiency (energy supply 0-4000 kJ · 24 h⁻¹), and less than 3-h sleep during the 7 days. Significant granulocytosis in combination with a lymphopenia in peripheral blood was observed during the whole course. A priming of the granulocytes for accentuated chemiluminescence response to SOZ was observed during the first days of the course with a maximal increase on day 3 in course A (+35% of control response) and on day 1 in course B (+ 12%). Thereafter, reduced responses to SOZ compared to control values (−28% and −21% in course A and B) were observed. In course A, a group (n = 8) receiving 5000 kJ · 24 h⁻¹ of additional energy, showed a more pronounced priming (maximum +57% versus +21 % of control response) during the first days. In course B, all the cadets had 3 h of organised rest/sleep on day 5, and a second priming of the chemiluminescence response was observed on the subsequent 2 days. These data indicated that moderate, continuous, predominantly aerobic physical activities for 1–3 days around the clock primed the production of reactive oxygen species in granulocytes. This priming may be beneficial for, for example, host defence against micro-organisms, but may also contribute to inflammatory damage to normal tissues such as muscle, tendons and joints during exercise. However, when the moderate exercise continued for several more days, a down-modulation of the granulocyte response was observed. The findings of this study further support the possibility that moderate physical activity stimulates immunity, while more extreme duration of the same activities may result in a down-modulation of nonspecific (and specific) immunity.     

一组分泌抗人粒细胞单克隆抗体杂交瘤细胞系的建立

用正常人的外周血粒细胞免疫Balb/c小鼠,取免疫脾细胞与小鼠骨髓瘤细胞系Sp2/0融合,用间接免疫荧光法及扁桃腺冰冻切片免疫过氧化物酶染色技术,从2次细胞融合中筛选并经克隆化得到一批稳定分泌抗粒细胞单抗的杂交瘤细胞系。对其中4株(FPMNI-FPMN4)杂交瘤细胞系所分泌的单抗作了系统的鉴定,证实它们是粒细胞特异性的单抗。     

Increased migration of neutrophils to granulocyte-colony stimulating factor in rat carrageenin-induced pleurisy: Roles of complement,bradykinin, and inducible cyclooxygenase-2

Administration of human recombinant granulocyte colony-stimulating factor (G-CSF, 100 g/kg/day, s.c) to rats for 4 days significantly increased circulating neutrophil counts (by 1130%), together with an increase in mononuclear leukocyte counts (by 119%). Infiltrated pleural neutrophil counts in G-CSF-treated rats (G-CSF-r) 5h after the intrapleural injection of zymosanactivated serum were significantly higher (by 155%) than those in control rats (Vehicle-r). In carrageenin-induced pleurisy, counts of infiltrated pleural neutrophils in G-CSF-r 5 and 7h after carrageenin were significantly higher (by 119% and 116%) than those in Vehicle-r. G-CSF treatment increased the volume of pleural exudate and the plasma exudation rate by 122% and 226%, compared to values in Vehicle-r 5h after carrageenin. Cobra venom factor (75 g/kg, i.v.) significantly reduced pleural neutrophil migration in G-CSF-r (by 53%) and Vehicle-r (by 49%). Bromelain (10 mg/kg, i.v.) and aspirin (100 mg/kg, p.o.) reduced pleural neutrophil migration and reduced exudate volume and plasma exudation. Intrapleural bradykinin-(1–5) and prostaglandin E₂ levels were significantly higher in G-CSF-r than in Vehicle-r. The increased neutrophil migration in G-CSF-r may be atributed to enhanced activation of the complement system facilitated by increased plasma exudation due to bradykinin and prostaglandins.accepted by M. J. Parnham     

卵巢癌抗独特型抗体/hGM-CSF融合蛋白质对体外免疫细胞的刺激作用

目的：探讨卵巢癌抗独特型单链抗体６Ｂ１１ｓｃＦｖ／ｈＧＭＣＳＦ融合蛋白质（６Ｂ１１ＧＭ）作为肿瘤疫苗的可能性。方法：采用体外Ｔ细胞增殖试验,对６Ｂ１１ＧＭ刺激Ｔ细胞的能力进行测定,并用流式细胞仪对Ｔ细胞表型及ＡＰＣＭＨＣⅡ表达情况进行测定,测定了外周血单个核细胞经６Ｂ１１ＧＭ激活后对卵巢癌细胞系的非ＭＨＣ限制的杀伤活性。结果：６Ｂ１１ＧＭ及６Ｂ１１均能引起特异的Ｔ细胞增殖,但６Ｂ１１ＧＭ组的增殖明显高于６Ｂ１１组,以ＣＤ４＋增殖为主。６Ｂ１１ＧＭ能明显增加抗原提呈细胞（ａｎｔｉｇｅｎｐｒｅｓｅｎｔｉｎｇｃｅｌ,ＡＰＣ）的ＭＨＣⅡ表达,使ＡＰＣ更有效地摄取抗原,激活非ＭＨＣ限制的杀伤活性。结论：６Ｂ１１ＧＭ能引起细胞免疫反应,作为疫苗具有良好的前景     

粒系集落刺激因子在恶性淋巴瘤治疗中的作用

观察粒系集落刺激因子（G-CSF）在恶性淋巴瘤治疗中的作用。对52例恶性淋巴瘤患者随机分为二组,27例接受化疗加G－CSF治疗,25例单独应用化疗．并对60岁以上老年患者另行分组进行研究。结果显示．G－CSF治疗组在白细胞和中性粒细胞降低持续时间、患者发热持续时间、化疗总疗程后延病例数及化疗总剂量减少病例数等方面均较对照组显著减少（P＜0.05～0.001）。但临床缓解率和2年生存率两组无明显差异。对60岁以上老年患者,G－CSF治疗可显著加快白细胞和中性粒细胞数的恢复．并明显减少化疗总疗程延及总剂量减少病例数。以上结果提示．G－CSF可有效恢复化疗所致的曰细胞和中性粒细胞减少,确保化疗能足量按时完成．将对恶性淋巴瘤的治疗尤其是老年患者的治疗产生有益作用。     

Recommendations on the use of colony-stimulating factors in children: conclusions of a European panel

During 1996 and 1997 a panel of European haematologists, oncologists, and neonatologists developed specific paediatric guidelines for the use of colony stimulating factors based on published literature and the clinical experience of these specialists within each of 13 countries. Well established indications for use comprise intervention in patients with life-threatening infection, adjunctive therapy post autologous bone marrow transplantation (BMT), mobilization of peripheral blood progenitor cells for autologous BMT, patients with acquired aplastic anaemia on anti-lymphocyte globulin and cyclosporin regimen, and severe congenital neutropenia. Less clear indications include primary prophylaxis to support dose intensification in children with high risk/advanced malignancies, secondary prophylaxis to prevent neutropenia in patients with a history of severe neutropenia, support therapy in cases of poor marrow function following BMT and for deteriorating marrow function following successful BMT, in neonatal sepsis and non infectious neonatal neutropenia, in drug induced neutropenia and in HIV-positive patients. Treatment is generally well tolerated and granulocyte colony stimulating factor appears better tolerated than granulocyte and macrophage colony stimulating factor. Economically colony stimulating factors have not been shown to induce excessive costs for a given patient. Conclusion In general the adult guidelines are applicable to children but additional considerations (aggressive or very progressive childhood neoplasms, specific indications, neonatal use, congenital disorders) must be taken into account. Received: 21 October 1997 and in revised form: 30 April 1998 /Accepted: 5 May 1998     

The effect of interleukin-6 on enhancing the invasiveness of head and neck cancer cells in vitro

Patients with head and neck cancers that produce a high concentration of granulocyte colony-stimulating factor (G-CSF) or patients with esophageal squamous cell carcinomas who have elevated serum interleukin-6 (IL-6) concentrations have been found previously to be at significant risk for tumor invasion to adjacent organs as well as frequent metastases. This suggests that G-CSF and Il-6 enhance the invasiveness and metastatic potential of cancer cells. We studied the in vitro invasiveness of head and neck cancer cell lines with and without recombinant human G-CSF (rhG-CSF) and human IL-6 (hIL-6) in an extracellular matrix membrane system. The degree of invasiveness was affected by incubating cells with hIL-6, but not by pre-incubating the cell-matrix with hIL-6. The maximum concentration of hIL-6 for enhanced invasiveness was approximately 5,000 u/ml. In addition, rhG-CSF enhanced the invasiveness of tumor cells that produced large amounts of G-CSF. The present study also suggests that tumor cells tend to invade and metastasize in an environment rich in hIL-6. Received: 3 November 1997 / Accepted: 1 April 1998     

Thrombopoietic factors potentially useful in the treatment of acute leukemia

Thrombocytopenia is a major cause of morbidity following intensive chemotherapy for acute leukemia. Over recent years, there has been an increasing use of platelet transfusions which, although generally efficacious to prevent severe hemorrhage, have associated risks of transmitting blood-borne disease and of alloimmunization. Therefore, there is a clinical requirement for a drug that will reliably alleviate the thrombocytopenia associated with leukemia therapy. The c-mpl ligand thrombopoietin is the most interesting factor for the treatment of thrombocytopenia because of its lineage specificity. Phase I and II studies confirm its biological efficacy to induce rise in platelet count in patients with solid tumors and acute leukemia. Several other pleiotropic hematopoietic growth factors are also currently in clinical trials. These include interleukin-6, interleukin-3, interleukin-11, PIXY321 and stem cell factor. The effects of these cytokines appear to be modest at most and, with the exception of interleukin-11, their side effects are likely to limit their clinical application. Combinations of factors may prove more efficacious approaches to enhance platelet recovery.     

粒细胞集落刺激因子刺激下急性白血病细胞增殖与其粒细胞集落刺激因子受体表达的研究

目的探讨粒细胞集落刺激因子(G-CSF)刺激下急性白血病(AL)细胞增殖与其粒细胞集落刺激因子受体(G-CS-FR)表达的关系。方法选初诊和难治复发的急性髓性白血病(AML)患者30例,急性淋巴细胞白血病(ALL)患者20例,正常对照组20例。化疗前留取骨髓5 m l,制备骨髓单个核细胞(MNC)悬液,并分别加入不同浓度的G-CSF(5,10,15,20,25 ng/m l),培养24h后用流式细胞技术检测其DNA倍体的量。同时选用G-CSFR、CD34的单抗,采用流式细胞技术检测G-CSFR、CD34在AL和正常粒细胞的表达情况。结果骨髓MNC培养24 h后各浓度的DNA倍体量在AML随着G-CSF浓度的增加有上升趋势,在ALL和正常对照无明显变化。G-CSFR、CD34的表达率:AML:(68.59±13.99)%,(45.15±4.22)%;ALL:(1.90±0.93)%,(46.75±3.15)%;正常对照:(70.5±10.8)%,(3.15±0.22)%。AML的G-CSFR表达率与ALL比较差异有统计学意义(P<0.05),与正常对照组差异无统计学意义(P>0.05);ALL的G-CSFR表达率与正常对照比较差异有统计学意义(P<0.05)。结论G-CSF可促进AML细胞增殖,不促进ALL细胞和正常粒细胞增殖;G-CSFR主要表达于成熟及恶性粒细胞,不表达于淋巴细胞。此结果在临床治疗白血病的过程中具有指导意义。