This paper is only available as a PDF. To read, Please Download here.
The charge-related determinants of albumin permeability have been the subject of much controversy. We have examined the permeability of either isolated glomerular basement membrane (GBM) or intact glomeruli in an in vitro filtration system to determine the effects of biochemical modifications selected to alter the molecules commonly implicated in restricting the glomerular permeability of anionic macromolecules such as albumin. Treatment of isolated GBM with heparatinase to remove heparan sulfate proteoglycan anionic side chains or profamine to effect charge neutralization had no effect on the albumin sieving coefficient. Protamine decreased hydraulic conductivity. pH titration to encompass the isoelectric point of GBM and albumin resulted in a modest increment in albumin permeability. In contrast, when intact glomeruli were treated with either heparatinase or protamine, albumin permeability doubled and protamine treatment of glomeruli resulted in an even greater augmentation of albumin permeability. These results suggest that, to the extent that in vitro GBM is similar to in vivo GBM, the restriction in albumin permeability due to glomerular charge requires the presence of glomerular cells.
Abbreviations:GBM (glomerular basement membrane), HSPG (heparan sulfate proteoglycan)
To read this article in full you will need to make a payment
Purchase one-time access:Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
One-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:Subscribe to Translational Research
Already a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
- Determinants of glomerular permselectivity: insights derived from observations in vivo.Kidney Int. 1977; 12: 229-237
- Biology of disease. Biophysiology of glomerular fitration and proteinuria.Lab Invest. 1984; 51: 7-21
- Anatomy of the kidney.in: Brenner BM Rector FR The Kidney. 3rd ed. Saunders, Philadelphia1986: 3
- Glomerular permeability. I. Ferritin transfer across the normal glomerular capillary wall.J Exp Med. 1961; 113: 47-91
- The distribution of albumin and immunoglobulin G in the glomerular capillary wall in aminonucleoside nephrosis.Pathology. 1978; 10: 335-347
- Increased permeability of the glomerular basement membrane to ferritin after removal of glycosaminoglycans (heparan sulfate) by enzyme digestion.J Cell Biol. 1980; 86: 688-691
- Macromolecular sieving by glomerular basement membrane in vitro: effect of polycation or biochemical modifications.Microvasc Res. 1991; 41: 311-327
- Influence of charge on fitration across renal basement membrane films in vitro.Kidney Int. 1984; 25: 527-533
- Glomerular basement membrane: in vitro studies of water and protein permeability.Am J Physiol. 1992; 262 (Renal Fluid Electrolyte Physiol 31): F919-F926
- A cytoskeleton-associated plasma membrane heparan sulfate proteoglycan in Schwann cells.J Biol Chem. 1986; 261: 7518-7525
- Partial characterization of heparan and dermatan sulfate proteoglycans synthesized by normal rat glomeruli.J Biol Chem. 1986; 261: 16636-16652
- Anti-DNA antibodies can bind to the glomerulus via two distinct mechanisms.Kidney Int. 1992; 42: 1363-1371
- Histones have high affinity for the glomerular basement membrane. Relevance for immune complex formation in lupus nephritis.J Exp Med. 1989; 169: 1879-1894
- Glomerular epithelium: structural alterations induced by polycations.Science. 1975; 189: 390-393
- Polycation-induced dislocation of slit diaphragms and formation of cell junctions in rat kidney glomeruli.Lab Invest. 1978; 39: 430-440
- Glomerular charge and urinary protein excretion: effects of systemic and intrarenal polycation infusion in the rat.Kidney Int. 1982; 22: 127-135
- Renal and systemic manifestations of glomerular disease.in: Brenner BM Rector FR The Kidney. 3rd ed. Saunders, Philadelphia1986: 903-906
- Removal of sulfated (heparan sulfate) or nonsulfated (hyaluronic acid) glycosaminoglycans results in increased permeability of the glomerular basement membrane to 125I-bovine serum albumin.Lab Invest. 1982; 47: 177-184
- Quantitative analysis of glomerular basement membrane glycosaminoglycans and evidence for their binding to adjacent cell membrane lipids.Anal Biochem. 1985; 145: 57-62
- Isolation and characterization of a rat lung fraction enriched in alveolar wall basement membranes.Exp Lung Res. 1985; 8: 15-28
- Glomerular permeabilily barrier in the rat. Functional assessment by in vitro methods.J Clin Invest. 1993; 92: 929-936
- Proteoglycans: structures and interactions.Annu Rev Biochem. 1991; 60: 443-475
- In vivo turnover of the basement membrane and other heparan sulfate proteoglycans of rat glomerulus.Arch Biochem Biophys. 1989; 269: 576-585
- Focal glomerular sclerosis in nephrotic patients: an electron microscopic study of glomerular podocytes.Kidney Int. 1975; 7: 111-122
- Glomerular epithelial abnormalities associated with the onset of proteinuria in aminonucleoside nephrosis.Am J Pathol. 1987; 126: 220-229
- Altered glomerular permeability as a result of focal detachmenl of the visceral epithelium.Kidney Int. 1982; 21: 565-574
- Distribution of anionic sites in glomerular basement membranes: their possible role in filtration and attachment.in: 2nd ed. Proc Natl Acad Sci. 73. 1976: 1646-1651
- Glomerular permeability. Transfer of native ferritin in glomeruli with decreased anionic sites.Lab Invest. 1978; 39: 547-553
- Measurement of albumin reflection coefficient with isolated rat glomeruli.J Am Soc Nephrol. 1992; 3: 1260-1269
- Identification and characterization of podocalyxin—the major sialoprotein of the renal glomerular epithelial cell.J Cell Biol. 1984; 98: 1591-1596
- Alterations in mesangial prostaglanding synthesis in mesangial cells.Biochim Biophys Acta. 1990; 1042: 221-226
- Effect of protamine sulfate on the permeability properties of the mammalian urinary bladder.J Membrane Biol. 1993; 133: 227-242
- Reversible hexadimethrine-induced alterations in glomerular structure and permeability.J Am Soc Nephrol. 1991; 1: 1095-1108
Accepted: February 9, 1994
Received in revised form: January 27, 1994
Received: June 18, 1993
☆Supported by the American Heart Association, Minnesota Affiliate.
☆Presented in part at the 1990 Meetings of the American Society of Nephrology and the American Federation for Clinical Research.
© 1994 Published by Elsevier Inc.