Persistence of DNA in the circulation of immunized rabbits.

The clearance of deoxyribonucleic acid (DNA) from the circulation was studied in non-immunized New Zealand rabbits and in rabbits immunized with heat-denatured, single-strand DNA (ss-DNA). Animals were injected intravenously with 1-3 mug/kg of 125-I-calf thymus ss-DNA. Initial clearance rates were -0.154 +/- 0.005 per cent (dose/ml/min) in non-immunized rabbits as compared to rates of -0.064 to -0.123 per cent (dose/ml/min) in rabbits immunized with ss-DNA. In immunized rabbits, clearance rates were inversely correlated with relative amounts of antibody, and increased amounts of circulating radiolabel were precipitable with 50 per cent saturated ammonium sulfate, suggesting binding to rabbit immunoglobulin. Thus, the presence of antibody to ss-DNA may delay the usually rapid clearance of ss-DNA from the blood. This observation is similar to that made for a variety of small molecular weight materials, such as insulin, digoxin, and morphine, and is in contrast to that for multivalent protein antigens, such as serum albumin and thyroglobulin. Persistence of DNA in the circulation may be important in the pathogenesis of DNA-anti-DNA-induced immune complex disease.