Devereux S, Porter J B, Hoyes K P, Abeysinghe R D, Saib R, Linch D C
Department of Haematology, University College and Middlesex Hospital School of Medicine, London.
Br J Haematol. 1990 Jan;74(1):17-23. doi: 10.1111/j.1365-2141.1990.tb02532.x.
The effects of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) on neutrophil lactoferrin (LF) and transcobalamin (TC) 1 and 3 secretion were determined in vitro and during in vivo administration in humans. In whole blood, in vitro incubation with GM-CSF reproducibly produced a rise in plasma LF concentration (P less than 0.05) whereas in purified neutrophils the results were variable. Exposure of whole blood to GM-CSF also resulted in a significant rise in plasma TC 1 and 3 (190 +/- 60%, P less than 0.05). The response was dose dependent with maximal effect at GM-CSF concentrations of 10 ng/ml and above. rhGM-CSF was administered on seven occasions to six patients with malignant disease prior to chemotherapy. Plasma LF and unsaturated TC 1 and 3 levels rose significantly in each patient studied and the rise coincided with the initial neutropenia due to margination that occurs during infusions of rhGM-CSF. Patients receiving rhGM-CSF may therefore have hypofunctional neutrophils due to secondary granule depletion.
在体外以及人体体内给药期间,测定了重组人粒细胞巨噬细胞集落刺激因子(rhGM-CSF)对中性粒细胞乳铁蛋白(LF)以及转钴胺素(TC)1和3分泌的影响。在全血中,与GM-CSF进行体外孵育可重复性地使血浆LF浓度升高(P<0.05),而在纯化的中性粒细胞中结果则存在差异。全血暴露于GM-CSF也导致血浆TC 1和3显著升高(190±60%,P<0.05)。该反应呈剂量依赖性,在GM-CSF浓度为10 ng/ml及以上时具有最大效应。在化疗前,对6例恶性疾病患者进行了7次rhGM-CSF给药。在所研究的每例患者中,血浆LF以及不饱和TC 1和3水平均显著升高,且这种升高与rhGM-CSF输注期间因边缘化而出现的初始中性粒细胞减少症相吻合。因此,接受rhGM-CSF治疗的患者可能由于次级颗粒耗竭而出现中性粒细胞功能低下。