Veerhuis R, van Es L A, Daha M R
Immunology. 1985 Apr;54(4):801-10.
Immune complexes are able to bind and activate the first component of complement, C1. Upon activation of C1, C1r and C1s are rapidly inactivated by C1-In which also forms a complex with these two subcomponents, resulting in their release from C1-immune aggregate complexes. The fate of C1q after the binding C1 to immune complexes in vivo is not clear and, therefore the clearance of radiolabelled rat C1q was investigated in normal rats and in rats receiving soluble aggregated human IgG. 125I-labelled rat C1q was cleared with a half-life (T 1/2) of 12.4 hr in normal rats. Injection of AIgG into rats that had previously received 125I-C1q accelerated the clearance of 125I-C1q, resulting, finally, in a T 1/2 of 53 min. The levels of circulating endogenous C1q were also followed using haemolytic titrations and immunochemical measurements. Directly after injection of AIgG into rats, there was a rapid decrease in C1q haemolytic activity to less than 25% of the initial value after 10 min. The rate of disappearance of C1q antigen, was, however, much slower, the lowest concentration being 30% at 2 hr. C1q haemolytic activity and the C1q antigen level returned to virtually normal values after 24 hr. Plasma samples were taken at different time intervals after the injection of AIgG and subjected to gel filtration on Sephacryl S-400 columns. It was found that, in the 10 min samples, C1q antigen and C1q haemolytic activity, each with an estimated molecular weight (MW) of 400,000, were detected together. In addition, there was C1q antigen with a MW of less than 69,000 without C1q haemolytic activity. SDS-PAGE analysis of the various serum samples indicated that the low MW C1q antigen had an apparent MW of 25,000. Measurement of uptake of 125I-C1q in various organs indicated that the main site of clearance of 125I-C1q is the liver.
免疫复合物能够结合并激活补体的第一成分C1。C1激活后,C1r和C1s会被C1抑制因子迅速灭活,C1抑制因子还会与这两个亚成分形成复合物,导致它们从C1 - 免疫聚集复合物中释放出来。体内C1q与免疫复合物结合后其命运尚不清楚,因此,研究了正常大鼠和接受可溶性聚集人IgG的大鼠中放射性标记的大鼠C1q的清除情况。在正常大鼠中,125I标记的大鼠C1q以12.4小时的半衰期(T1/2)被清除。给先前接受过125I - C1q的大鼠注射聚集人IgG(AIgG)加速了125I - C1q的清除,最终导致半衰期为53分钟。还使用溶血滴定和免疫化学测量来跟踪循环内源性C1q的水平。在给大鼠注射AIgG后,C1q溶血活性迅速下降,10分钟后降至初始值的不到25%。然而,C1q抗原的消失速度要慢得多,2小时时最低浓度为30%。24小时后,C1q溶血活性和C1q抗原水平几乎恢复到正常值。在注射AIgG后的不同时间间隔采集血浆样本,并在Sephacryl S - 400柱上进行凝胶过滤。发现在10分钟的样本中,检测到了估计分子量(MW)为400,000的C1q抗原和C1q溶血活性。此外,存在分子量小于69,000且无C1q溶血活性的C1q抗原。对各种血清样本的SDS - PAGE分析表明,低分子量C1q抗原的表观分子量为25,000。对125I - C1q在各种器官中的摄取测量表明,125I - C1q清除的主要部位是肝脏。