一种可与凝血因子 VIII 活性分离的凝血因子 VIII 制剂成分会下调人类单核细胞功能。

A component of factor VIII preparations which can be separated from factor VIII activity down modulates human monocyte functions.

作者信息

Eibl M M, Ahmad R, Wolf H M, Linnau Y, Götz E, Mannhalter J W

出版信息

Blood. 1987 Apr;69(4):1153-60.

Abstract

In this study we investigated different aspects of monocyte functions following interaction of monocytes (Mo) with therapeutic concentrations of factor VIII (F VIII) concentrate. A short (one-hour) treatment of normal Mo with F VIII concentrates led to a significant (P less than 0.001) down modulation of Fc receptors expressed in the Mo plasma membrane. This down modulation was accompanied by a decrease of Mo effector functions that was expressed by a reduced capacity of F VIII-treated Mo to release O2 radicals (40% of controls) and to kill bacteria (% killing: control Mo, 65%; F VIII-treated Mo, 24% to 51%). Further studies showed that the modulating activity was due to a contaminant present in F VIII concentrates (immune complexes or IgG aggregates). Fractionation using molecular sieving revealed that the modulatory activity was confined to a high-molecular range fraction (Mr greater than 1,270,000 daltons), while the fraction containing monomeric IgG had no effect. Further fractionation by affinity chromatography on protein A-Sepharose separated the coagulation activity (effluent) from the Mo function-modulating activity (eluate). We conclude that treatment with F VIII concentrates might contribute to an immunocompromised state in some hemophiliacs and facilitate opportunistic infections in these patients.

摘要

在本研究中，我们调查了单核细胞（Mo）与治疗浓度的凝血因子 VIII（F VIII）浓缩物相互作用后单核细胞功能的不同方面。用 F VIII 浓缩物对正常单核细胞进行短时间（1 小时）处理，导致单核细胞质膜上表达的 Fc 受体显著下调（P 小于 0.001）。这种下调伴随着单核细胞效应功能的降低，表现为经 F VIII 处理的单核细胞释放 O2 自由基的能力降低（为对照的 40%）以及杀灭细菌的能力降低（杀灭率：对照单核细胞为 65%；经 F VIII 处理的单核细胞为 24%至 51%）。进一步研究表明，调节活性是由于 F VIII 浓缩物中存在的一种污染物（免疫复合物或 IgG 聚集体）。使用分子筛进行分级分离显示，调节活性局限于高分子量范围的级分（Mr 大于 1,270,000 道尔顿），而含有单体 IgG 的级分没有作用。通过蛋白 A - 琼脂糖亲和色谱进一步分级分离，将凝血活性（流出物）与单核细胞功能调节活性（洗脱物）分开。我们得出结论，用 F VIII 浓缩物治疗可能会导致一些血友病患者出现免疫功能低下状态，并促进这些患者发生机会性感染。