TY - JOUR
T1 - Glomerular localization of circulating single-stranded DNA in mice. Dependence on the molecular weight of DNA
AU - Carlson, Jeanine A.
AU - Hodder, Stuart R.
AU - Ucci, Angelo A.
AU - Madaio, Michael P.
N1 - Funding Information:
This work was supported in part by grants from the Lupus Foundation of America and the United States Public Health Service (AM33694). We thank Dr Nicolaos Madias for his review of the manuscript and Dr Robert S. Schwartz for his advice and support.
PY - 1988/6
Y1 - 1988/6
N2 - 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.
AB - 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.
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U2 - 10.1016/0896-8411(88)90029-7
DO - 10.1016/0896-8411(88)90029-7
M3 - Article
C2 - 3251491
AN - SCOPUS:0024033078
SN - 0896-8411
VL - 1
SP - 231
EP - 241
JO - Journal of Autoimmunity
JF - Journal of Autoimmunity
IS - 3
ER -