Increased permeability of the glomerular basement membrane to ferritin after removal of glycosaminoglycans (heparan sulfate) by enzyme digestion.
TLDR
It is demonstrated that removal of heparan sulfate (but not other GAG) leads to a dramatic increase in the permeability of the GBM to NF.Abstract:
Glomerular basement membranes (GBM's) were subjected to digestion in situ with glycosaminoglycan-degrading enzymes to assess the effect of removing glycosaminoglycans (GAG) on the permeability of the GBM to native ferritin (NF). Kidneys were digested by perfusion with enzyme solutions followed by perfusion with NF. In controls treated with buffer alone, NF was seen in high concentration in the capillary lumina, but the tracer did not penetrate to any extent beyond the lamina rara interna (LRI) of the GBM, and litte or no NF reached the urinary spaces. Findings in kidneys perfused with Streptomyces hyaluronidase (removes hyaluronic acid) and chondroitinase-ABC (removes hyaluronic acid, chondroitin 4- and 6-sulfates, and dermatan sulfate, but not heparan sulfate) were the same as in controls. In kidneys digested with heparinase (which removes most GAG including heparan sulfate), NF penetrated the GBM in large amounts and reached the urinary spaces. Increased numbers of tracer molecules were found in the lamina densa (LD) and lamina rara externa (LRE) of the GBM. In control kidneys perfused with cationized ferritin (CF), CF bound to heparan-sulfate rich sites demonstrated previously in the laminae rarae; however, no CF binding was seen in heparinase-digested GBM's, confirming that the sites had been removed by the enzyme treatment. The results demonstrated that removal of heparan sulfate (but not other GAG) leads to a dramatic increase in the permeability of the GBM to NF.read more
Citations
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Matrix Proteoglycans: From Molecular Design to Cellular Function
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References
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Anionic sites in the glomerular basement membrane. In vivo and in vitro localization to the laminae rarae by cationic probes.
Yashpal S. Kanwar,M G Farquhar +1 more
TL;DR: The experiments demonstrate the existence of a quasi- regular, lattice-like network of anionic sites in the LRI and LRE and the mesangial matrix, demonstrable in vivo (by CF binding), in fixed kidneys (by RR staining), and in isolated GBM's ( by CF binding).
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TL;DR: Urine formation begins at the walls of theglomerular capillaries with the separation of as much as a third of the plasma entering the glomeruli of each kidney into a solution having...
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Role of molecular charge in glomerular permeability. Tracer studies with cationized ferritins.
TL;DR: Mouse kidneys were perfused with Krebs-Ringer bicarbonate buffer containing native, anionic horse spleen ferritin or various cationized derivatives, and the glomerular localization of the probe molecules determined by electron microscopy suggested that intrinsic negative charges are present in the GBM and endothelium.
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THE PERMEABILITY OF GLOMERULAR CAPILLARIES TO GRADED DEXTRANS : Identification of the Basement Membrane as the Primary Filtration Barrier
TL;DR: The basement membrane is the main glomerular permeability barrier to dextrans, and (since their behavior is known to be similar) to proteins of comparable dimensions (40,000–200,000 mol wt).
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