Teeling J L, De Groot E R, Eerenberg A J, Bleeker W K, Van Mierlo G, Aarden L A, Hack C E
Central Laboratory of The Netherlands Red Cross Blood Transfusion Service, Academic Medical Centre, University of Amsterdam.
Clin Exp Immunol. 1998 Nov;114(2):264-70. doi: 10.1046/j.1365-2249.1998.00697.x.
IVIG preparations have biological effects in vivo that are not fully understood. Possible effects include the property to stimulate Fc receptors on various cell types. To study whether IVIG may interact with neutrophils we developed an in vitro system, in which neutrophils, in whole blood or purified, were incubated with IVIG and assessed for degranulation by measuring the release of elastase and lactoferrin in culture medium. All commercially available IVIG preparations tested induced degranulation of neutrophils when incubated for 2 h at therapeutically relevant concentrations. In studies with blocking antibodies against Fc receptors (FcR), this degranulation was shown to be dependent on Fc gammaRII, whereas Fc gammaRIII had no effect. Experiments with purified neutrophils as well as binding experiments with labelled IVIG preparations indicated that neutrophil degranulation resulted from a direct interaction of IVIG with neutrophils. Using gel filtration fractions, it was found that polymeric and dimeric IgG present in IVIG was mainly responsible for the degranulation. We suggest that degranulation of neutrophils may contribute to the (side)effects of IVIG treatment in vivo.
静脉注射免疫球蛋白（IVIG）制剂在体内具有尚未完全明确的生物学效应。可能的效应包括刺激多种细胞类型上的Fc受体的特性。为了研究IVIG是否可能与中性粒细胞相互作用，我们开发了一种体外系统，在该系统中，将全血或纯化后的中性粒细胞与IVIG一起孵育，并通过测量培养基中弹性蛋白酶和乳铁蛋白的释放来评估脱颗粒情况。所有测试的市售IVIG制剂在治疗相关浓度下孵育2小时后均诱导中性粒细胞脱颗粒。在使用抗Fc受体（FcR）阻断抗体的研究中，这种脱颗粒显示依赖于FcγRII，而FcγRIII没有影响。使用纯化中性粒细胞的实验以及与标记IVIG制剂的结合实验表明，中性粒细胞脱颗粒是IVIG与中性粒细胞直接相互作用的结果。通过凝胶过滤分级分离发现，IVIG中存在的多聚体和二聚体IgG主要负责脱颗粒。我们认为中性粒细胞脱颗粒可能导致IVIG治疗在体内产生（副）效应。
