Binding of double-stranded DNA to glomeruli of rats in vivo

Abstract

In vivo binding of double-stranded DNA (dsDNA) to renal glomeruli of rats was examined. 125I-dsDNA (600 basepairs) was perfused with 131I-IgG as a blood marker into the right renal artery of normal rats, and blood flow was restored. After 10 minutes, isolated glomeruli showed a specific uptake of DNA, which increased in a saturable fashion with increasing doses of administered DNA. To exclude the possibility that 125I in the glomeruli represented only DNA breakdown products, we extracted the DNA from the glomeruli for analysis by polyacrylamide gel electrophoresis. The extracted DNA was 120-200 bp in size, which is large enough to bind antibodies to DNA. In contrast, the radioactivity of DNA taken up by the liver or renal tissues other than glomeruli was predominantly trichloroacetic acid soluble, i.e., less than 15 bp. Immunofluorescence studies showed that antibodies to DNA, administered after DNA, were present in glomeruli. Our data indicate that dsDNA binds to glomeruli in vivo in a saturable manner, and remains large enough to be antigenic. Therefore, the binding of DNA to glomeruli, followed by interaction with antibodies to dsDNA may be a mechanism for DNA-anti-DNA complex formation in glomeruli in patients with systemic lupus erythematosus.