Gorgani N N, Altin J G, Parish C R
Division of Immunology and Cell Biology, The John Curtin School of Medical Research, Australian National University, Canberra, ACT, Australia.
Immunology. 1999 Nov;98(3):456-63. doi: 10.1046/j.1365-2567.1999.00885.x.
In previous studies we have shown that histidine-rich glycoprotein (HRG), a relatively abundant plasma protein, can bind to immunoglobulin G (IgG) and inhibit the insolubilization of IgG-containing immune complexes (IC). It was of interest, therefore, to determine whether HRG can inhibit the formation of insoluble IC (IIC) resulting from the interaction of rheumatoid factor (RF) with human IgG-containing IC. Light scattering techniques were used to examine the effect of HRG on the formation of IIC between RF and IC containing human IgG according to three different models. In all three models physiological concentrations of HRG could block the formation of IIC induced by RF. Optical biosensor studies of the RF-IgG interaction also revealed that HRG can mask the epitopes on IgG recognized by RF. Additional studies examined whether HRG can solubilize already formed IIC and demonstrated that HRG can, in fact, partially solubilized IIC. These data indicate that HRG can regulate the formation of IIC induced by RF at three levels: namely by inhibiting the initial recognition of IgG containing IC by RF, by inhibiting the subsequent insolubilization of IgG containing IC by RF and by solubilizing already formed IIC. Collectively, these findings suggest that HRG may be an important inhibitor of the formation of pathogenic IC in diseases such as systemic lupus erythematosus and rheumatoid arthritis.
在先前的研究中，我们已经表明，富含组氨酸的糖蛋白（HRG）是一种相对丰富的血浆蛋白，它可以与免疫球蛋白G（IgG）结合，并抑制含IgG的免疫复合物（IC）的不溶性。因此，确定HRG是否能够抑制类风湿因子（RF）与含人IgG的IC相互作用所导致的不溶性IC（IIC）的形成是很有意义的。根据三种不同模型，使用光散射技术来检测HRG对RF与含人IgG的IC之间IIC形成的影响。在所有这三种模型中，生理浓度的HRG都能够阻断RF诱导的IIC的形成。对RF-IgG相互作用的光学生物传感器研究还表明，HRG能够掩盖RF识别的IgG上的表位。另外的研究检测了HRG是否能够使已经形成的IIC溶解，并证明HRG实际上能够部分溶解IIC。这些数据表明，HRG可以在三个水平上调节RF诱导的IIC的形成：即通过抑制RF对含IgG的IC的初始识别，通过抑制RF对含IgG的IC的后续不溶性化，以及通过溶解已经形成的IIC。总的来说，这些发现提示，HRG可能是系统性红斑狼疮和类风湿关节炎等疾病中致病性IC形成的重要抑制剂。
