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Lactoferrin interacts with deoxyribonucleic acid: a preferential reactivity with double-stranded DNA and dissociation
Abstract:
LF was found to bind to deoxyribonucleic acid as assessed by immunofluorescence studies on cell nuclei, affinity chromatography of DNA on immobilized LF, and gel chromatography of an LF-DNA reaction mixture. LF immobilized on Sepharose 4-B was reacted with 125I-labeled DNA in both its double-stranded and single-stranded configurations; dsDNA eluted with a 0.69M NaCl buffer, whereas ssDNA eluted with a 0.25M NaCl buffer. Additional evidence for a preferential reactivity with dsDNA was provided by the enzymatic treatment of preformed dsDNA-LF and ssDNA-LF complexes with S1 endonuclease, and DNAse 1--DNase digestion alone liberated free LF. The interaction of LF with DNA partially inhibited the binding of anti-DNA antibodies from patients with SLE, as assayed in a standard Farr assay. Furthermore, DNA-anti-DNA (labeled with 125I-IgG) complexes could be dispersed in vitro by the addition of LF. It is hypothesized that the release of LF by neutrophils chemotactically attracted to DNA-anti-DNA complexes may act as a feedback loop to modulate the inflammatory response in SLE.