A key role for fibronectin in the sequential binding of native dsDNA and monoclonal anti-DNA antibodies to components of the extracellular matrix: its possible significance in glomerulonephritis.

The interactions of DNA, monoclonal anti-DNA autoantibodies and isolated purified components of the extracellular matrix (ECM) were studied in a solid phase model system. Binding of DNA to each of the components was assessed using monoclonal antibody and enzyme conjugated antiglobulin in direct binding and inhibition assays. Each of the genetically distinct collagens (Types I-IV), proteoglycan monomer and laminin, bound ssDNA, but dsDNA bound significantly only to fibronectin. When used in an inhibition system, fibronectin linked DNA and anti-DNA antibodies to the collagens; it had a differential effect on the binding of ssDNA and dsDNA to a Type IV collagen matrix, the most striking feature being a 100 fold increase in dsDNA binding to Type IV collagen in the presence of fibronectin. It is likely that fibronectin binds dsDNA to collagen by separate binding domains for these molecules, and that this may be involved in the deposition of DNA in kidneys in some forms of glomerulonephritis.