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In vitro demonstration of a particular affinity of glomerular basement membrane and collagen for DNA. A possible basis for a local formation of DNA-anti-DNA complexes in systemic lupus erythematosus

Miescher, P. A.
Published in Journal of Experimental Medicine. 1976, vol. 144, no. 2, p. 428-443
Abstract In vitro, collagen and collagen-like material in GBM, were demonstrated to have a particular high affinity for any DNA tested (mammalian, bacterial, viral, and plant). GBM fixed DNA 40-80 times more than HGG and BSA and 10-40 times more than bacterial LPS. GBM has a higher affinity for SSDNA than for DSDNA. This binding was inhibited at low pH, low ionic strength, and in the presence of anionic detergents, indicating that the highly negatively charged DNA may interact with the basic site on collagen or GBM by electrostatic forces. This interaction was competitively interfered with by DNA-binding proteins such as Clq. Complexes formed of DNA and anti-DNA antibodies did not exhibit the same binding property as free DNA. However, DNA which was already bound to GBM or to collagen could very efficiently bind anti-DNA antibodies and form immune complexes which would remain on these structures. The biological significance of the binding of DNA to GBM or to collagen should be particularly considered in relation to the pathogenesis of SLE. It is possible that DNA released from disrupted or degenerating cells would bind to surrounding collagen fibers or to basement membranes and then act as an immunoabsorbant for circulating anti-DNA antibodies. Some evidence for an in vivo binding of SSDNA to renal structures was obtained in mice treated with bacterial LPS 2 days before the injection of SSDNA.
Keywords AnimalsAntigen-Antibody ComplexBasement Membrane/metabolismBinding SitesCollagen/ metabolismComplement C1/metabolismDNA/immunology/ metabolismDNA, Single-Stranded/metabolismHumansHydrogen-Ion ConcentrationKidney Glomerulus/ metabolismLupus Erythematosus, Systemic/immunologyMiceOsmolar ConcentrationProtein BindingSolubilityTemperature
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PMID: 8578
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