Iida K, Whitlow M B, Nussenzweig V
Department of Pathology, New York University Medical Center, NY 10016.
J Immunol. 1991 Oct 15;147(8):2638-42.
Nucleated cells can resist attack by C by exocytosis or endocytosis of the terminal C components C5b-9 (membrane attack complex) (MAC), but it is generally accepted that formation of a single MAC channel on E leads to lysis (one-hit theory). We find that human and guinea pig E, but not SRBC, can eliminate the MAC from the membrane in the form of microvesicles and escape destruction. When guinea pig or human E are incubated with C5b-9, vesiculation proceeds without a lag and is detected at nonlytic doses of C9. Continuous Ca2+ influx is required for vesiculation. The amount of released vesicles is in direct relation to Ca2+ concentration, and the increase in vesiculation is associated with a parallel decrease in lysis. SRBC, which do not vesiculate when Ca2+ loaded, are lysed by C5b-9 with the same efficiency in the presence or absence of Ca2+. Vesicles released from guinea pig RBC under C5b-9 attack are enriched in C9 by a factor of 10, compared with the unlysed cells, and by a factor of 3 to 4, compared with ghosts. We conclude that E are protected from lysis not only by CD59 and C8bp/HRF, which prevent MAC assembly, but also by selective elimination of the MAC.
有核细胞可通过胞吐作用或胞吞作用清除终末补体成分C5b-9（膜攻击复合物，MAC）来抵抗补体（C）的攻击，但人们普遍认为，在红细胞（E）上形成单个MAC通道会导致细胞溶解（一击理论）。我们发现，人及豚鼠的E细胞而非绵羊红细胞（SRBC），能够以微泡形式从细胞膜上清除MAC并避免被破坏。当豚鼠或人的E细胞与C5b-9孵育时，微泡形成无延迟，且在非溶解剂量的C9时即可检测到。微泡形成需要持续的钙离子内流。释放的微泡数量与钙离子浓度直接相关，微泡形成增加与细胞溶解的平行减少相关。加载钙离子时不形成微泡的SRBC，在有无钙离子存在的情况下被C5b-9溶解的效率相同。与未溶解的细胞相比，豚鼠红细胞在C5b-9攻击下释放的微泡中C9含量富集10倍，与空泡相比富集3至4倍。我们得出结论，E细胞不仅通过阻止MAC组装的CD59和C8bp/HRF得到保护以免于溶解，还通过对MAC的选择性清除得到保护。
