Veerhuis R, Van Es L A, Daha M R
Eur J Immunol. 1985 Sep;15(9):881-7. doi: 10.1002/eji.1830150904.
Earlier studies have indicated that C1q, the first subcomponent of complement component C1, is bound to lymphocytes via specific C1q receptor sites. We have recently shown that adherent guinea pig peritoneal exudate macrophages express specific receptors for C1q (Veerhuis, R. et al., Immunology 1985. 54: 801). The present studies were performed to determine whether binding of 125I-labeled human C1q (125I-C1qhu) to adherent guinea pig peritoneal exudate macrophages would also result in ingestion and subsequent degradation of 125I-C1qhu. The binding of 125I-C1qhu to adherent peritoneal macrophages at 4 degrees C is inhibited fully not only by C1qhu and guinea pig C1q (C1qgp) but also by pepsin fragments of C1qhu. The amount of trichloroacetic acid nonprecipitable radioactivity that appeared in the supernatant was used as a measure for the degradation of 125I-C1qhu. 125I-C1qhu is degraded initially into fragments of 25 kDa, after which it is degraded further into small molecular weight peptides. Ingestion of 125I-C1q by the macrophages occurs before the 125I-C1q is degraded. In the presence of limited amounts of soluble aggregates of guinea pig IgG2 (AIgG), a known activator of C1, part of the C1q is bound to the AIgG and all of the AIgG in turn is bound to the cellular Fc receptors leading to an enhanced binding of 125I-C1q to the cells, a binding that was maximal at near equimolar concentrations of 125I-C1qhu and 131I-AIgG. In the presence of a 30-fold excess of AIgG, however, only a small percentage of the AIgG binds to cellular Fc receptors and the interaction of C1q with its receptor is decreased due to competitive inhibition. The results presented in this report thus suggest that free C1q may be eliminated by specific interaction with C1q receptors present on circulating and tissue phagocytoses and, in addition, that in the presence of immune complexes modulation of elimination of C1q may be encountered.
早期研究表明，补体成分C1的首个亚成分C1q通过特定的C1q受体位点与淋巴细胞结合。我们最近发现，贴壁的豚鼠腹腔渗出液巨噬细胞表达C1q的特异性受体（维尔胡伊斯，R.等人，《免疫学》1985年。54:801）。进行本研究以确定125I标记的人C1q（125I-C1qhu）与贴壁的豚鼠腹腔渗出液巨噬细胞结合是否也会导致125I-C1qhu的摄取及随后的降解。4℃时125I-C1qhu与贴壁腹腔巨噬细胞的结合不仅完全受到人C1q（C1qhu）和豚鼠C1q（C1qgp）的抑制，还受到C1qhu的胃蛋白酶片段的抑制。上清液中出现的三氯乙酸不可沉淀放射性量用作125I-C1qhu降解的指标。125I-C1qhu最初降解为25 kDa的片段，之后进一步降解为小分子量肽。巨噬细胞摄取125I-C1q发生在125I-C1q降解之前。在有限量的豚鼠IgG2可溶性聚集体（AIgG，一种已知的C1激活剂）存在的情况下，部分C1q与AIgG结合，而所有的AIgG又与细胞Fc受体结合，导致125I-C1q与细胞的结合增强，这种结合在125I-C1qhu和131I-AIgG接近等摩尔浓度时达到最大。然而，在AIgG过量30倍的情况下，只有一小部分AIgG与细胞Fc受体结合，并且由于竞争性抑制，C1q与其受体的相互作用减弱。本报告中的结果因此表明，游离的C1q可能通过与循环和组织吞噬细胞上存在的C1q受体的特异性相互作用而被清除，此外，在存在免疫复合物的情况下，可能会遇到C1q清除的调节。
