Glomerular localization of circulating single-stranded DNA in mice. Dependence on the molecular weight of DNA

Although it has been observed that DNA has a high binding affinity for the glomerular basement membrane (GBM) in vitro, glomerular localization of DNA has not been demonstrated in vivo. To evaluate this possibility, after injection of ¹²⁵I ssDNA of varying molecular weight (mol. wt.) to normal mice, we measured glomerular levels of DNA in vivo. Following administration of 2 mg of ¹²⁵I high mol. wt. purified single stranded(ss) DNA (2-6 kilobases; 0.7-2.0 × 10⁶D) to normal mice, DNA was not detected in glomeruli, despite measurable blood levels of DNA for 72 h. In contrast, after injection of 280 μg of low mol. wt. ¹²⁵ssDNA (160-200 bases; mol. wt. = 5.3-6.6 × 10⁴D) to normal mice, glomerular localization was observed throughout the 24-h study period despite relatively low ¹²⁵IssDNA blood levels. The results of these studies indicate that free circulating DNA can bind to sites within glomeruli in vivo, and that the size of DNA is crucial for this interaction. Since low mol. wt. DNA is present in the plasma of patients with active lupus, these findings raise the possibility that DNA may bind to glomeruli and serve as a planted antigen for in situ immune complex formation with circulating anti-DNA antibodies.