Inhibitory effect of lysozyme on the intraglomerular immune complex formation in lupus mice.
The effect of lysozyme on intraglomerular immune complex deposition was examined in NZB/W F1 mice undergoing unilateral nephrectomy. Unilateral nephrectomy enhanced the glomerular immune complex deposition and glomerular lesions, which were suppressed by repeated intraperitoneal injections of lysozyme, in spite of unaltered serum anti-DNA antibody titers. DNA binding to the glomerular basement membrane (GBM) examined in vitro and that to glomeruli examined in vitro were also suppressed by lysozyme. An increased survival rate and decreased proteinuria were also induced by this basic protein. The mechanisms of the ameliorative effect were studied in vitro. DNA was bound to the GBM only in the presence of serum, plasma, or fibronectin. A similar inhibitory effect on DNA binding was also obtained by another polycation, hexadimethrine, in place of lysozyme. The in vitro findings suggest that DNA binding to the GBM is mediated by fibronectin, and that lysozyme electrostatically inhibits this binding, thereby possibly reducing the in situ DNA-anti-DNA complex formation in the GBM.
Yamamoto
T
T
First Department of Medicine, Hamamatsu University School of Medicine, Japan.
Nagase
M
M
Honda
N
N
D000419:Albuminuria; D000818:Animals; D000936:Antigen-Antibody Complex; D001323:Autoantibodies / Q000032:analysis; D001485:Basement Membrane / Q000276:immunology / Q000378:metabolism; D004247:DNA / Q000276:immunology; D005353:Fibronectins / Q000502:physiology; D066298:In Vitro Techniques; D007678:Kidney Glomerulus / Q000473:pathology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000473:pathology; D008181:Lupus Nephritis / Q000473:pathology / Q000503:physiopathology*; D051379:Mice; D009113:Muramidase / Q000494:pharmacology*
D000936:Antigen-Antibody Complex; D001323:Autoantibodies; D005353:Fibronectins; D004247:DNA; D009113:Muramidase