Gavin A L, Wines B D, Powell M S, Hogarth P M
Helen M. Schutt Laboratory for Immunology, Austin Research Institute, Austin Hospital, Heidelberg, Victoria, Australia.
Clin Exp Immunol. 1995 Dec;102(3):620-5. doi: 10.1111/j.1365-2249.1995.tb03862.x.
Control of IgG immune complex formation and deposition is important in determining the nature and extent of subsequent immune effector responses, and appears to be aberrant in some autoimmune diseases. In this study we demonstrate that recombinant soluble Fc gamma RII (rsFc gamma RII) is an effective modulator of immune complex formation, delaying immune precipitation in a manner which is dose-dependent, and can be specifically inhibited by anti-Fc gamma RII MoAb Fab' fragments. This inhibitory role in immune precipitation also provides a possible mechanistic explanation for our previous demonstration of the efficacy of rsFc gamma RII as an inhibitor of immune complex-induced inflammation in the Arthus reaction in vivo. RsFc gamma RII inhibited immune complex precipitation in two different experimental systems. First, rsFc gamma RII inhibited the precipitation of 125I-bovine serum albumin (BSA)-anti-BSA complexes in a dose-dependent manner, while an irrelevant protein (soybean trypsin inhibitor) had no effect on the precipitation of the immune complexes. Moreover, rsFc gamma RII inhibited the precipitation of ovalbumin (OVA)-anti-OVA complexes as determined by turbidimetric analysis, where the inhibition of immune complex precipitation by rsFc gamma RII was dose-dependent and was specifically blocked by prior incubation with Fab' fragments of a blocking MoAb to Fc gamma RII. RsFc gamma RII could inhibit the precipitation of BSA-anti-BSA complexes in the presence of excess bystander IgG and did not inhibit complement-mediated prevention of immune precipitation, demonstrating that rsFc gamma RII did not block C1 binding to the BSA-anti-BSA complex. Unlike complement, rsFc gamma RII could not cause re-solubilization of pre-formed precipitated BSA-anti-BSA complexes. Soluble Fc gamma Rs have been detected in biological fluids of normal and inflammatory disease patients, yet the role of sFc gamma R is still unclear. However, they now play a potential role in the modulation of immune complex solubility.
控制IgG免疫复合物的形成和沉积对于确定后续免疫效应反应的性质和程度很重要，并且在某些自身免疫性疾病中似乎存在异常。在本研究中，我们证明重组可溶性FcγRII（rsFcγRII）是免疫复合物形成的有效调节剂，以剂量依赖的方式延迟免疫沉淀，并且可以被抗FcγRII单克隆抗体Fab'片段特异性抑制。其在免疫沉淀中的这种抑制作用也为我们之前证明rsFcγRII作为体内Arthus反应中免疫复合物诱导的炎症抑制剂的功效提供了一种可能的机制解释。RsFcγRII在两种不同的实验系统中抑制免疫复合物沉淀。首先，rsFcγRII以剂量依赖的方式抑制125I-牛血清白蛋白（BSA）-抗BSA复合物的沉淀，而一种无关蛋白（大豆胰蛋白酶抑制剂）对免疫复合物的沉淀没有影响。此外，通过比浊分析确定，rsFcγRII抑制卵清蛋白（OVA）-抗OVA复合物的沉淀，其中rsFcγRII对免疫复合物沉淀的抑制是剂量依赖的，并且通过与抗FcγRII阻断单克隆抗体的Fab'片段预先孵育而被特异性阻断。RsFcγRII可以在存在过量旁观者IgG的情况下抑制BSA-抗BSA复合物的沉淀，并且不抑制补体介导的免疫沉淀预防，这表明rsFcγRII不阻断C1与BSA-抗BSA复合物的结合。与补体不同，rsFcγRII不能使预先形成的沉淀BSA-抗BSA复合物重新溶解。在正常和炎症性疾病患者的生物体液中已检测到可溶性FcγR，但sFcγR的作用仍不清楚。然而，它们现在在调节免疫复合物溶解度方面发挥着潜在作用。
