Histone mediates glomerular deposition of small size DNA anti-DNA complex

Abstract

Histone can mediate the binding of free DNA to the glomerular capillary wall. We tested whether histone could mediate the deposition of preformed DNA-anti-DNA immune complex (IC). IC were generated using monoclonal anti-DNA Ab and excess of small size 125I-DNA; after further digestion with DNase the IC, containing 5 micrograms DNA (now 20 to 60 bp), was injected into the left kidney of rats. When given alone, only about 0.2% of the IC bound in glomeruli. Prior injection of 200 micrograms of core histones (H2A,H2B,H3,H4) resulted in high glomerular binding of the IC; 18.1% of the injected dose (measured as 125I-DNA) was bound at 15 minutes. Mouse immunoglobulin, representing the IC, could be seen in a capillary pattern. C3 was also present in a similar pattern, showing that complement had been activated. Discrete electron-dense deposits were seen in a subendothelial and subepithelial localization at 15 minutes. Although about 1 microgram of DNA was deposited in the glomeruli, it could not be detected by indirect immunofluorescence or intercalating dyes. These studies provide direct evidence that histones can mediate the binding of particular circulating DNA-anti-DNA immune complexes to the glomerular capillary wall in vivo. If small size DNA fragments (< 100 bp) are involved in lupus nephritis, our results provide a possible explanation for the frequent failure to detect DNA deposits in renal biopsies from SLE patients.