Streptococcal protein H forms soluble complement-activating complexes with IgG, but inhibits complement activation by IgG-coated targets
Streptococcal protein H forms soluble complement-activating complexes with IgG, but inhibits complement activation by IgG-coated targets
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DOI：
10.1074/jbc.272.33.20774
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发表时间：
1997-08-15
影响因子：
4.8
通讯作者：
Bjorck, L
中科院分区：
文献类型：
--
作者：
Berge, A;Kihlberg, BM;Bjorck, L
蛋白H是与IgG的恒定Fc区相互作用的化脓性链球菌的表面蛋白，已知通过细菌产生的半胱氨酸蛋白酶从链球菌表面释放。链球菌感染后肾小球肾炎和风湿热的条件下，免疫复合物和自身免疫机制已被建议发挥致病作用，本研究表明，除了蛋白H的人血清产生补体激活与剂量依赖性裂解C3。这种激活是IgG依赖性的，是IgG和蛋白H之间形成复合物的结果。这些复合物的大小不均匀，分子量为400 kDa至1.4 MDa。使用补体耗尽的血清与补体蛋白重建，蛋白H的激活被认为是依赖于经典的，但独立的补体的替代途径。与基于可溶性蛋白H IgG复合物的实验结果相反，当IgG固定在表面上时，补体活化被蛋白H抑制。C1 q和免疫球蛋白之间的相互作用代表经典途径活化的第一步，并且蛋白H有效地抑制C1 q与固定在聚丙烯酰胺珠上的IgG的结合，蛋白H减少了C3在IgG包被的珠上的沉积，并抑制IgG致敏的红细胞的免疫溶血。最后，与缺乏蛋白H的同基因突变细菌的表面相比，在表达蛋白II的野生型链球菌的表面上沉积的C3显著更少，结果表明，从链球菌表面释放的蛋白H IgG复合物可以在感染部位产生补体分解，而细菌表面的补体活化被抑制，这对宿主-寄生虫关系具有重要意义。可溶性蛋白H IgG复合物可能有助于链球菌感染的免疫并发症。
Protein H, a surface protein of Streptococcus pyogenes interacting with the constant Fc region of IgG, is known to be released from the streptococcal surface by a cysteine proteinase produced by the bacteria. Poststreptococcal glomerulonephritis and rheumatic fever are conditions in which immune complexes and autoimmune mechanisms have been suggested to play pathogenetic roles, The present study demonstrates that addition of protein H to human serum produces complement activation with dose-dependent cleavage of C3. The activation was IgG-dependent and the result of complexes formed between IgG and protein H. These complexes were size heterogeneous with molecular masses of 400 kDa to 1.4 MDa. Using complement-depleted serum reconstituted with complement proteins, the activation by protein H was found to be dependent of the classical, but independent of the alternative pathway of complement. In contrast to results of experiments based on soluble protein H IgG complexes, complement activation was inhibited by protein H when IgG was immobilized on a surface, The interaction between C1q and immunoglobulins represents the first step in the activation of the classical pathway, and protein H efficiently inhibited the binding of C1q to IgG immobilized on polyacrylamide beads, Protein H reduced C3 deposition on the IgG-coated beads and inhibited immune hemolysis of IgG-sensitized erythrocytes, Finally, significantly less C3 was deposited on the surface of protein II-expressing wild-type streptococci than on the surface of isogenic mutant bacteria devoid of protein H, The results demonstrate that protein H IgG complexes released from the streptococcal surface can produce complement breakdown at the sites of infection, whereas complement activation on bacterial surfaces is inhibited, This should have important implications for host-parasite relationships, In addition, soluble protein H IgG complexes might contribute to immunological complications of streptococcal infections.