Interaction of fibronectin with DNA/anti-DNA complexes from systemic lupus erythematosus: role of activated complement Cl in modulation of the interactions.
Fibronectin (Fn) is an integral constituent of the endothelial cell surface and the basement membrane. The mechanism for binding DNA/anti-DNA complexes to Fn was examined in a solid-phase assay. In physiological buffer, a low-affinity binding of DNA was observed with Fn and optimal binding was seen at pH 6.5 and in the absence of Ca2+. Further, the interaction of DNA to Fn was inhibited when DNA was complexed to anti-DNA antibody. However, complement Clq mediated the binding of complexes to Fn at pH 7.4 and it was proportional to the extent of the dissociation of Cl. Cl inactivator (Cl-In) appeared to play a modulating role; whereas at low concentrations (Cl:Cl-In::4: less than 1) it enhanced the binding of complexes to Fn, higher concentrations inhibited the binding. Further, sera from patients with active systemic lupus erythematosus reacted with Fn, which was shown to be dependent on the presence of Clq and was minimally affected by DNase treatment of sera, indicating a relatively minor role of DNA in the direct binding of DNA to Fn. These findings support "circulating immune complex" hypothesis in the pathogenesis of lupus glomerular immune complex deposition disease.
Gupta
R C
RC
Department of Medicine, University of Tennessee, Memphis.
Simpson
W A
WA
Raghow
R
R
D000974:Antibodies, Antinuclear / Q000378:metabolism*; D000936:Antigen-Antibody Complex; D003166:Complement Activating Enzymes / Q000494:pharmacology; D003167:Complement Activation; D003172:Complement C1 / Q000276:immunology* / Q000494:pharmacology; D015922:Complement C1q; D004247:DNA / Q000276:immunology* / Q000378:metabolism; D004347:Drug Interactions; D005353:Fibronectins / Q000378:metabolism*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000378:metabolism*
D000974:Antibodies, Antinuclear; D000936:Antigen-Antibody Complex; D003172:Complement C1; D005353:Fibronectins; D015922:Complement C1q; D004247:DNA; D003166:Complement Activating Enzymes