Jones F S, Pisetsky D S, Kurlander R J
Clin Immunol Immunopathol. 1986 Apr;39(1):49-60. doi: 10.1016/0090-1229(86)90204-7.
To study the assembly of DNA-anti-DNA complexes in vivo, we have measured the clearance from blood and organ localization of a murine IgG2a monoclonal anti-DNA antibody, called 6/0, following the infusion of DNA intravenously or intraperitoneally. Intraperitoneal DNA caused a profound acceleration of 6/0 anti-DNA clearance that was dose dependent and demonstrable after the infusion of as little as 1.9 microgram per gram of body weight of single-stranded DNA. The antibody was cleared primarily in the liver without increased deposition in the kidney. Intraperitoneal infusions of DNA also accelerated the clearance of 6/0 in autoimmune MRL-lpr/lpr mice. In contrast, intravenous DNA given in comparable doses caused only a slight increase in 6/0 antibody clearance; this accelerated clearance was seen only at low antigen doses and only during the first 10 min following DNA infusion. Using double-radiolabeling techniques, 6/0 and Cl.18, an IgG2ak myeloma protein without anti-DNA activity, were found to disappear from blood at a comparable rate in both B6D2 mice and MRL-lpr/lpr mice. These results suggest that the DNA-anti-DNA immune complexes can form in vivo but that this process is profoundly affected by the manner in which DNA enters the circulation. In addition, the results suggest that DNA-dependent clearance is not a major pathway for anti-DNA metabolism in normal or at least one strain of autoimmune mice.
为了研究DNA-抗DNA复合物在体内的组装情况,我们在静脉内或腹腔内注入DNA后,测量了一种名为6/0的鼠源IgG2a单克隆抗DNA抗体从血液中的清除率以及在器官中的定位。腹腔内注入DNA导致6/0抗DNA清除率显著加快,这是剂量依赖性的,在注入低至每克体重1.9微克的单链DNA后即可显现。抗体主要在肝脏中清除,肾脏中的沉积并未增加。腹腔内注入DNA也加速了自身免疫性MRL-lpr/lpr小鼠体内6/0的清除。相比之下,以相当剂量静脉内注入DNA仅导致6/0抗体清除率略有增加;这种加速清除仅在低抗原剂量下以及DNA注入后的前10分钟内可见。使用双放射性标记技术发现,在B6D2小鼠和MRL-lpr/lpr小鼠中,6/0和无抗DNA活性的IgG2ak骨髓瘤蛋白Cl.18从血液中消失的速率相当。这些结果表明,DNA-抗DNA免疫复合物可在体内形成,但该过程受到DNA进入循环方式的深刻影响。此外,结果表明,在正常或至少一种自身免疫性小鼠品系中,DNA依赖性清除不是抗DNA代谢的主要途径。