Fernie-King B A, Seilly D J, Willers C, Würzner R, Davies A, Lachmann P J
Microbial Immunology Group, Centre for Veterinary Science, University of Cambridge; Institute for Hygiene and Social Medicine, Leopold Franzens University, Innsbruck, Austria.
Immunology. 2001 Jul;103(3):390-8. doi: 10.1046/j.1365-2567.2001.01249.x.
Streptococcal inhibitor of complement (SIC) was first described in 1996 as a putative inhibitor of the membrane attack complex of complement (MAC). SIC is a 31 000 MW protein secreted in large quantities by the virulent Streptococcus pyogenes strains M1 and M57, and is encoded by a gene which is extremely variable. In order to study further the interactions of SIC with the MAC, we have made a recombinant form of SIC (rSIC) in Escherichia coli and purified native M1 SIC which was used to raise a polyclonal antibody. SIC prevented reactive lysis of guinea pig erythrocytes by the MAC at a stage prior to C5b67 complexes binding to cell membranes, presumably by blocking the transiently expressed membrane insertion site on C7. The ability of SIC and clusterin (another putative fluid phase complement inhibitor) to inhibit complement lysis was compared, and found to be equally efficient. In parallel, by enzyme-linked immunosorbent assay both SIC and rSIC bound strongly to C5b67 and C5b678 complexes and to a lesser extent C5b-9, but only weakly to individual complement components. The implications of these data for virulence of SIC-positive streptococci are discussed, in light of the fact that Gram-positive organisms are already protected against complement lysis by the presence of their peptidoglycan cell walls. We speculate that MAC inhibition may not be the sole function of SIC.
链球菌补体抑制剂（SIC）于1996年首次被描述为补体膜攻击复合物（MAC）的一种假定抑制剂。SIC是一种分子量为31000的蛋白质，由强毒化脓性链球菌M1和M57菌株大量分泌，由一个极具变异性的基因编码。为了进一步研究SIC与MAC的相互作用，我们在大肠杆菌中制备了重组形式的SIC（rSIC），并纯化了天然M1 SIC，用于制备多克隆抗体。SIC在C5b67复合物结合到细胞膜之前的阶段阻止了MAC对豚鼠红细胞的反应性溶解，推测是通过阻断C7上瞬时表达的膜插入位点。比较了SIC和聚集素（另一种假定的液相补体抑制剂）抑制补体溶解的能力，发现它们同样有效。同时，通过酶联免疫吸附测定，SIC和rSIC都与C5b67和C5b678复合物强烈结合，与C5b - 9的结合较弱，但与单个补体成分的结合仅为弱阳性。鉴于革兰氏阳性菌已经通过其肽聚糖细胞壁的存在而免受补体溶解的影响，讨论了这些数据对SIC阳性链球菌毒力的影响。我们推测MAC抑制可能不是SIC的唯一功能。
