Chang N S, Leu R W, Rummage J A, Anderson J K, Mole J E
Guthrie Research Institute, Laboratory of Molecular Immunology, Guthrie Medical Center, Sayre, Pennsylvania 18840.
Immunology. 1992 Dec;77(4):532-8.
Regulation of macrophage Fc receptor (Fc gamma R)-mediated phagocytic function by histidine-rich glycoprotein (HRG) was investigated. Pretreatment of oil-elicited inflammatory mouse peritoneal macrophages with HRG for 1-3 hr increased their Fc gamma R-mediated binding and phagocytosis of IgG-opsonized sheep erythrocyte conjugates (EA). A significant reduction of Fc gamma R-dependent EA binding and phagocytosis occurred after pretreatment of macrophages with HRG for more than 8 hr. These results indicate that HRG is capable of modulating Fc gamma R expression in a biphasic fashion, which directly affects the overall efficiency of phagocytosis. HRG differentially regulated the functions of Fc gamma R subclasses. For example, HRG reduced the efficiency of Fc gamma RII (Fc gamma 2b/gamma 1R)-dependent phagocytosis of erythrocytes conjugated with monoclonal IgG2b or IgG1 by macrophages pretreated with HRG for 24 hr. However, when similar studies were performed using erythrocytes coated with monoclonal IgG2a, HRG was less effective in inhibiting Fc gamma RI (Fc gamma 2aR)-dependent phagocytosis. As an HRG-binding glycosaminoglycan, heparin failed to block the regulatory function of HRG on macrophages. Similarly, interferon-gamma (IFN-gamma) was not capable of blocking the functional activity of HRG. These studies suggest that HRG regulates macrophage function via a novel pathway different from that of heparin or IFN-gamma.
研究了富含组氨酸糖蛋白（HRG）对巨噬细胞Fc受体（FcγR）介导的吞噬功能的调节作用。用HRG对油诱导的炎症小鼠腹腔巨噬细胞进行1 - 3小时预处理，可增加其FcγR介导的对IgG调理的绵羊红细胞结合物（EA）的结合和吞噬作用。在用HRG对巨噬细胞进行超过8小时的预处理后，FcγR依赖性EA结合和吞噬作用显著降低。这些结果表明，HRG能够以双相方式调节FcγR的表达，这直接影响吞噬作用的整体效率。HRG对FcγR亚类的功能有不同的调节作用。例如，HRG降低了经24小时HRG预处理的巨噬细胞对与单克隆IgG2b或IgG1结合的红细胞的FcγRII（Fcγ2b/γ1R）依赖性吞噬效率。然而，当使用包被有单克隆IgG2a的红细胞进行类似研究时，HRG在抑制FcγRI（Fcγ2aR）依赖性吞噬作用方面效果较差。作为一种HRG结合糖胺聚糖，肝素未能阻断HRG对巨噬细胞的调节功能。同样，干扰素-γ（IFN-γ）也不能阻断HRG的功能活性。这些研究表明，HRG通过一条不同于肝素或IFN-γ的新途径调节巨噬细胞功能。
