Gresham H D, Clement L T, Lehmeyer J E, Griffin F M, Volanakis J E
J Immunol. 1986 Aug 1;137(3):868-75.
Human neutrophil Fc receptor-mediated phagocytosis can be markedly enhanced by a low m.w. (less than 10,000) heat-labile cytokine(s) derived from specifically stimulated human mononuclear cells and from a human T cell line, MO(t). PMN incubated with supernatant from control mononuclear leukocyte (MNL) culture bound EIgG (percentage of rosettes = 73.7% +/- 7.1) but did not ingest the attached targets (phagocytic index, PI = 40.7 +/- 9.5) as efficiently as PMN incubated with supernatant from adherent MNL, which had ingested EIgG and were then cocultured with nonadherent MNL (PI = 264.3 +/- 46.3). Cytokine-containing supernatants were fractionated on YM-10 Centricon microconcentrators, and the effluent (YM-10E) was found to contain the phagocytosis-enhancing activity. Optimal Fc receptor-mediated ingestion by YM-10E-stimulated PMN required a critical level of target-bound IgG; stimulation was dose dependent and detectable after 5 min at 37 degrees C with a maximal response by 15 min. Monoclonal antibody 3G8 (anti-PMN Fc receptor) inhibited in a dose-dependent fashion both Fc receptor-mediated rosette formation and ingestion by nonstimulated and YM-10E-stimulated PMN. Solid-phase 3G8 Fab had the same effect. A previously undescribed monoclonal antibody, 1C2, exhibited a different pattern of inhibition. It had no effect on rosetting or ingestion of EIgG by nonstimulated PMN; however, it inhibited EIgG phagocytosis by YM-10E-stimulated PMN down to the level of nonstimulated ingestion without affecting rosette formation. Solid-phase 1C2 had the same effect. These data indicate that phagocytosis mediated by 3G8-positive Fc receptors may be enhanced by cytokine(s) stimulation in a manner requiring the molecule recognized by 1C2. Monoclonal antibodies to the alpha-chain of CR3 had only minimal effects on YM-10E-stimulated ingestion. Fluorescence flow cytometry of YM-10E-stimulated PMN, indirectly stained with 3G8 or 1C2, indicated that cytokine enhancement of EIgG ingestion occurred without an increase in either 3G8 or 1C2 binding sites. These data show that the low avidity Fc receptor, which binds immune complexes, may be functionally modulated at sites of inflammation where PMN and macrophages mediate clearance and destruction of immune complexes and opsonized particles.
人中性粒细胞Fc受体介导的吞噬作用可被一种低分子量（小于10,000）的热不稳定细胞因子显著增强，该细胞因子来源于特异性刺激的人单核细胞和人T细胞系MO(t)。与对照单核白细胞（MNL）培养上清共孵育的PMN结合了EIgG（玫瑰花结百分比 = 73.7% +/- 7.1），但吞噬附着靶标的效率不如与贴壁MNL上清共孵育的PMN，后者已吞噬EIgG并随后与非贴壁MNL共培养（吞噬指数，PI = 264.3 +/- 46.3）。含细胞因子的上清在YM - 10中空纤维浓缩器上进行分级分离，发现流出物（YM - 10E）含有增强吞噬作用的活性。YM - 10E刺激的PMN进行最佳Fc受体介导的摄取需要靶标结合的IgG达到临界水平；刺激呈剂量依赖性，在37℃下5分钟后可检测到，15分钟时达到最大反应。单克隆抗体3G8（抗PMN Fc受体）以剂量依赖性方式抑制Fc受体介导的玫瑰花结形成以及未刺激和YM - 10E刺激的PMN的摄取。固相3G8 Fab具有相同的效果。一种先前未描述的单克隆抗体1C2表现出不同的抑制模式。它对未刺激的PMN结合EIgG或摄取EIgG没有影响；然而，它将YM - 10E刺激的PMN吞噬EIgG的能力抑制到未刺激摄取的水平，而不影响玫瑰花结形成。固相1C2具有相同的效果。这些数据表明，由3G8阳性Fc受体介导的吞噬作用可能通过细胞因子刺激以一种需要1C2识别的分子的方式增强。针对CR3α链的单克隆抗体对YM - 10E刺激的摄取只有最小的影响。用3G8或1C2间接染色的YM - 10E刺激的PMN的荧光流式细胞术表明，细胞因子增强EIgG摄取的过程中，3G8或1C2的结合位点均未增加。这些数据表明，结合免疫复合物的低亲和力Fc受体可能在炎症部位发生功能调节，在该部位PMN和巨噬细胞介导免疫复合物和调理颗粒的清除与破坏。
