We studied the effect of fibronectin (FN) on aggregates at 30 minutes (mean 2 SD 15 f 1.7%) than did the normal rats (T, 1.5 f 0.2 minutes, 22 f 2.870, respectively; P < 0.0005). Both parameters were within normal limits in the FN-treated rats (Tn 1.6 +-0.4 minutes, 22 +-6%. respectively). In vitro, FN induced a significant increase in aggregated IgC catabolism by Kupffer cells and peritoneal macrophages from normal rats. These results show that FN reduces the proteinuria and histologic lesions of chronic nephritis in rats. These beneficial effects of FN could be due to the improved clearance of immune complexes, decreased glomerular deposition, and perhaps, to better renal processing of immune complexes.Fibronectin ( F N ) is a high molecular weight glycoprotein (440 kd) composed of 2 similar polypeptide chains that are connected by 2 disulfide bonds (1). It is present both in a soluble form in extracellular fluids and in an insoluble form in connective tissue and basement membranes. where it acts as a binding or attachment protein. FN manifests a high affinity for native and denatured collagen, DNA, fibrin, hyaluronic acid, heparin. and several bacterial species ( 2 ) . This protein also mediates cell adhesion, migration, and mobility. and functions as an opsonic probe for fibrin. collagen, and cytoskeletal debris, preventing excessive localization in highly vascular organs such as the lungs and kidneys (3).The mononuclear phagocyte system plays a major role in the clearance of circulating immune complexes (CIC). Kupffer cells represent the predominant mononuclear phagocytic cells that clear foreign material from the blood (4.5). The removal of CIC is mediated by the Fc and CRI receptors on these cells. When large amounts of immune complexcs saturate
We measured plasma fibronectin levels by a rocket immunoelectrophoresis in rats with chronic serum sickness induced by repeated injections of ovalbumin and in rats with epithelial nephropathy induced by a single injection of adriamycin. In the early phases of the immune model, rats presented granular deposits of IgG in the mesangial area with no or descrete proteinuria (less than 40 mg/24 h). Fibronectin levels in that group were significantly higher (450 +/- 90 micrograms/mL) than in normal rats of the same age (350 +/- 46; p less than 0.01). When animals presented IgG deposits in the capillary wall, an important nephrotic syndrome developed in most of them. Fibronectin levels then increased very significantly (863 +/- 153 micrograms/mL; p less than 0.0005). In the model of adriamycin nephropathy, fibronectin significantly increased (580 +/- 110 micrograms/mL; p less than 0.0005) from the first week, when proteinuria was in a range 40-60 mg/24 h. However, the levels were higher (860 +/- 175 micrograms/mL; p less than 0.0005) when a complete nephrotic syndrome developed. At this time, plasma fibronectin levels correlated directly in both models with the degree of proteinuria and inversely with the total serum protein concentration. Our results show that plasma fibronectin levels increased very early in animals with immune and toxic damage of the kidney. The highest elevated values found thereafter, when a full nephrotic syndrome was present, suggest an increased synthetic rate of that glycoprotein linked to that situation.
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