Vossebeld P J, Homburg C H, Roos D, Verhoeven A J
Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, University of Amsterdam, The Netherlands.
Int J Biochem Cell Biol. 1997 Mar;29(3):465-73. doi: 10.1016/s1357-2725(96)00160-4.
Human neutrophils express two types of Fc gamma receptors, the transmembrane Fc gamma RIIa and the glycan-phosphatidylinositol-anchored Fc gamma RIIIb, that show synergism in provoking a cellular response. To analyse further the requirements for this synergism to occur we used the monoclonal antibody 3G8, directed against Fc gamma RIII. This antibody is able to induce neutrophil activation, as measured by an increase in the intracellular free Ca2+ concentration and homotypic neutrophil aggregation, but only when the Fc part of the antibody is able to interact with Fc gamma RIIa. We observed that binding of the Fab parts of 3G8 mAb to two Fc gamma RIIIb molecules and binding of the Fc part to one Fc gamma RIIa molecule is required, because a bispecific antibody, 2B1, in which only one 3G8 Fab is present, did not induce neutrophil activation. Moreover, engagement of one Fc gamma RIIa molecule and two Fc gamma RIIb molecules on the same cell is instrumental to achieve activation of the mAb 3G8. The activation of neutrophils by the 3G8 antibody represents a further example of synergistic activation of neutrophils via Fc gamma receptors.
人类中性粒细胞表达两种类型的Fcγ受体，即跨膜的FcγRIIa和糖基磷脂酰肌醇锚定的FcγRIIIb，它们在引发细胞反应时表现出协同作用。为了进一步分析这种协同作用发生的条件，我们使用了针对FcγRIII的单克隆抗体3G8。该抗体能够诱导中性粒细胞活化，通过细胞内游离Ca2+浓度的增加和同型中性粒细胞聚集来衡量，但前提是抗体的Fc部分能够与FcγRIIa相互作用。我们观察到，3G8单克隆抗体的Fab部分与两个FcγRIIIb分子结合以及Fc部分与一个FcγRIIa分子结合是必需的，因为仅存在一个3G8 Fab的双特异性抗体2B1不会诱导中性粒细胞活化。此外，同一细胞上一个FcγRIIa分子和两个FcγRIIIb分子的结合对于实现单克隆抗体3G8的活化至关重要。3G8抗体对中性粒细胞的活化代表了通过Fcγ受体协同激活中性粒细胞的又一个例子。
