Granulocyte concentrates: prolonged functional capacity during storage in the presence of phenotypic changes

Granulocyte concentrates: prolonged functional capacity during storage in the presence of phenotypic changes
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DOI:
10.3324/haematol.12489
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发表时间:
2008-07-01
期刊:
HAEMATOLOGICA-THE HEMATOLOGY JOURNAL
影响因子:
--
通讯作者:
Kuijpers, Taco W.
Kuijpers, Taco W.
中科院分区:
其他
文献类型:
--
作者:
Drewniak, Agata;Boelens, Jaap-Jan;Kuijpers, Taco W.

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背景粒细胞输注已被提议作为一种过渡性治疗方案,用于治疗长期化疗引起的中性粒细胞减少症患者,这些患者患有严重的真菌和细菌感染。为了恢复,当患者对标准治疗难治时,需要足够数量的粒细胞。本研究的目的是评估粒细胞集落刺激因子/地塞米松动员的粒细胞用于transfusions.Design and MethodsGranulocytes的功能特点和疗效从白细胞分离产品进行了测试的细胞表面抗原的表达,与内皮细胞的相互作用,运动,杀死微生物和生存。粒细胞用于输血在16个重症儿童,谁是-除了一个病人的粒细胞功能障碍-所有患有长期neutralization.ResultsMobilization的粒细胞与粒细胞集落刺激因子和地塞米松引起的表型变化(CD 62 L表达下降,CD 66 b和CD 177水平增加)在体内。粒细胞与内皮细胞相互作用(滚动,粘附,迁移)和杀死各种类型的病原体的能力不受动员,白细胞分离和辐射程序的影响。即使在储存24小时后,粒细胞在功能上与从未处理供体分离的粒细胞没有区别。粒细胞输注似乎有利于70%的患者,16名儿童中有11人表现出临床恢复后1-2周内开始transfusions.ConclusionsAlthough CD 62 L表达下调用于粒细胞输注的粒细胞,伴随的CD 177上调可以解释完整的相互作用与内皮细胞。测试的所有其他粒细胞功能都完好无损,包括杀死真菌的能力。粒细胞浓缩物可储存至少24小时而不丧失体外活力和功能。如体内试验所示,粒细胞输注可能是一种有效的治疗患有危及生命的感染的贫血儿科患者的方法。
BackgroundGranulocyte transfusion has been proposed as a bridging therapy for patients with prolonged periods of chemotherapy-induced neutropenia, who suffer from severe fungal and bacterial infections. To recover, adequate numbers of granulocytes are required when the patients are refractory to standard treatment. The aim of this study was to assess the functional characteristics and efficacy of granulocyte colony-stimulating factor/ dexa methasone-mobilized granulocytes used for transfusions.Design and MethodsGranulocytes from the leukapheresis products were tested for the expression of cell-surface antigens, interactions with endothelial cells, motility, killing of microbes and survival. The granulocytes were used in vivo for transfusion in 16 severely ill children, who were - apart from a patient with a granulocyte dysfunction - all suffering from prolonged neutropenia.ResultsMobilization of granulocytes with granulocyte colony-stimulating factor and dexamethasone caused phenotypic changes (decreased CD62L expression and increased levels of CD66b and CD177). The ability of the granulocytes to interact with endothelial cells (rolling, adhesion, transmigration) and to kill various types of pathogens was not affected by the mobilization, leukapheresis and irradiation procedures. The granulocytes were functionally indistinguishable from those isolated from untreated donors, even after 24 hours of storage. Granulocyte transfusion seemed to benefit 70% of patients, as 11 out of the 16 children showed clinical recovery within 1-2 weeks after beginning the transfusions.ConclusionsAlthough CD62L expression is downregulated on granulocytes used for granulocyte transfusions, concomitant CD177 upregulation may explain the intact interactions with endothelial cells. All other granulocyte functions tested were intact, including the ability to kill fungi. Granulocyte concentrates can be stored without loss of in vitro viability and functionality for at least 24 hours. As demonstrated in vivo, granulocyte transfusions may be an effective therapy for neutropenic pediatric patients suffering from life-threatening infections.