Medical Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institute, 171 77 Stockholm, Sweden.
Proc Natl Acad Sci U S A. 2013 Jun 18;110(25):10252-7. doi: 10.1073/pnas.1301480110. Epub 2013 May 13.
A unique anti-inflammatory property of IgG, independent of antigen specificity, is described. IgG with modification of the heavy-chain glycan on asparagine 297 by the streptococcal enzyme endo-β-N-acetylglucosaminidase (EndoS) induced a dominant suppression of immune complex (IC)-mediated inflammation, such as arthritis, through destabilization of local ICs by fragment crystallizable-fragment crystallizable (Fc-Fc) interactions. Small amounts (250 µg) of EndoS-hydrolyzed IgG were sufficient to inhibit arthritis in mice and most effective during the formation of ICs in the target tissue. The presence of EndoS-hydrolyzed IgG disrupted larger IC lattice formation both in vitro and in vivo, as visualized with anti-C3b staining. Neither complement binding in vitro nor antigen-antibody binding per se was affected.
描述了 IgG 的一种独特的抗炎特性，这种特性不依赖于抗原特异性。通过链球菌酶内切-β-N-乙酰氨基葡萄糖苷酶（EndoS）修饰 IgG 重链上的天门冬酰胺 297 的聚糖，可通过 Fc-Fc 相互作用使局部免疫复合物（IC）不稳定，从而诱导免疫复合物（IC）介导的炎症的主要抑制作用，如关节炎。少量（250µg）的内切-β-N-乙酰氨基葡萄糖苷酶处理的 IgG 即可抑制小鼠关节炎，并且在靶组织中形成 IC 时最有效。用抗 C3b 染色观察到，内切-β-N-乙酰氨基葡萄糖苷酶处理的 IgG 存在时，无论是在体外还是在体内，均会破坏较大的 IC 晶格形成。既不影响体外补体结合，也不影响抗原-抗体结合本身。
