Glomerular Sialoprotein

Mohos, Steven C.; Skoza, L

doi:10.1126/science.164.3887.1519

Cited by 124 publications

(54 citation statements)

References 21 publications

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“…Loss of such fixed negative charges has also been shown to be associated with proteinuria in several experimental glomerular diseases (2,3,7,31,32). Although anionic sites occur on the surfaces of both endothelium and epithelium (6,17,23,24,(31)(32)(33)43), the available evidence indicates that the GBM serves as both the charge and the size barrier in the filtration of macromolecules since all anionic proteins or neutral particles used as tracers (anionic ferritin [12,37], endogenous albumin [39], catalase [40], and neutral dextrans of varying size [55-78 A,] (5, 10)) do not penetrate beyond the LRI under normal flow conditions. The role of the GBM as the charge barrier was demonstrated directly by the experiments of Rennke et al (36,37) which showed that ferritin penetrates the GBM in increasing amounts the greater the isoelectric point.…”

Section: Possible Functions Of the Anionic Sitesmentioning

confidence: 99%

Anionic sites in the glomerular basement membrane. In vivo and in vitro localization to the laminae rarae by cationic probes.

Kanwar

Farquhar

1979

The Journal of Cell Biology

508

200

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Cationized ferritin (CF) of narrow pI range (7.3-7.5) and the basic dye ruthenium red (RR) have been used as cationic probes to partially characterize anionic sites previously demonstrated in the glomerular basement membrane (GBM). When CF was given i.v. to normal rats and the left kidney was fixed by perfusion 15 min thereafter, clusters of CF molecules were found throughout the lamina rara interna (LRI), lamina rara externa (LRE), and mesangial matrix distributed at regular (-60 nm) intervals. When kidneys were perfused with aldehyde fixative containing RR, small (20 nm) RR-stained particles were seen in the same locations distributed with the same 60 nm repeating pattern, forming a quasiregular, lattice-like arrangement. Fine (-3 nm) filaments connected the sites and extended between them and the membranes of adjoining endothelial and epithelial cells 9 When CF was given i.v. followed by perfusion with RR in situ, both probes localized to the same sites 9 CF remained firmly bound after prolonged perfusion with 0.1-0 9 M KCI or NaCI. It was displaced by perfusion with buffers of high ionic strength (0 9149 M KCI) or pH (<3.0 or >10.0). CF also bound (clustered at -60 nm intervals) to isolated GBM's, and binding was lost when such isolated GBM's were treated with buffers of high ionic strength or pH. These experiments demonstrate the existence of a quasi-regular, lattice-like network of anionic sites in the LRI and LRE and the mesangial matrix 9 The sites are demonstrable in vivo (by CF binding), in fixed kidneys (by RR staining), and in isolated GBM's (by CF binding). The results obtained with CF show that the binding of CF (and probably also RR) to the laminae rarae is electrostatic in nature since it is displaced by treatment with buffers of high ionic strength or pH. With RR the sites resemble in morphology and staining properties the proteoglycan particles found in connective tissue matrices and in association with basement membranes in several other locations 9 KEY WORDS cationized ferritin red proteoglycans 9 ionic interaction isolated GBM's 9 ruthenium Recent studies have shown that the glomerular capillary wall contains fixed negatively charged sites which may be important in maintaining nor- J. CELL BIOLOGY 9The Rockefeller University Press 9

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Section: Possible Functions Of the Anionic Sitesmentioning

confidence: 99%

Anionic sites in the glomerular basement membrane. In vivo and in vitro localization to the laminae rarae by cationic probes.

Kanwar

Farquhar

1979

The Journal of Cell Biology

508

200

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“…Sialyl residues have been found in all three layers of the capillary wall. They have been detected in isolated glomerular basement membranes (GBM) (8)(9)(10) and in association with the cell membranes of both the endothelium (11)(12) and epithelium (4)(5)(6)(7)11), where they are part of the sialic acid-rich, cell-surface coats. A colloidal iron-stainable, cell-coat material is particularly concentrated on the epithelium.…”

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confidence: 99%

“…As far as the negative biochemical results are concerned, the explanation may lie in the fact that previous analyses for uronic acid (8,9) or sulfate groups (8) have been done on isolated GBM prepared by sonication, which, according to our experience, disrupts the anionic sites or, if prolonged, removes them entirely. Previous histochemical studies had the disadvantage that they were done on fixed sections (4)(5)(6)(7)(11)(12) incubated in basic dyes (with and without prior enzyme digestion). In such preparations it was difficult to make a clear distinction between the charged sites in the laminae rarae and those on the adjacent endothelial and epithelial cell membranes.…”

mentioning

confidence: 99%

Presence of heparan sulfate in the glomerular basement membrane

Kanwar

Farquhar

1979

Proc. Natl. Acad. Sci. U.S.A.

495

191

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The glomerular basement membrane was subjected to digestion with specific enzymes to determine the chemical nature (sialoglycoproteins, collagenous peptides, or glycosaminoglycans) of the anionic sites previously demonstrated in the laminae rarae. Enzyme digestion was carried out both in situ and in vitro. Kidneys were perfused in situ with enzyme solutions followed by perfusion with fixative containing the cationic dye, ruthenium red, to detect the anionic sites. Glomerular basement membranes were isolated by detergent treatment of glomeruli and incubated with enzyme solutions, followed by incubation with cationized ferritin (pI 7.3-7.5 Physiologic studies have established that the glomerular capillaries function as a size-and charge-selective barrier in the production of the glomerular filtrate and in the retention of plasma proteins in the circulation (1-3). By inference it has been assumed (1-3) that charge selectivity is due to the presence in the glomerulus of fixed negative charges, but their precise nature and location in the capillary wall have not been established. Since macromolecular compounds carrying sialic acid residues have been-up to recently-the only known polyanions present in the glomerulus, they have been considered the most likely candidates responsible for the charge barrier (1, 2, 4-7). Sialyl residues have been found in all three layers of the capillary wall. They have been detected in isolated glomerular basement membranes (GBM) (8-10) and in association with the cell membranes of both the endothelium (11-12) and epithelium (4-7, 11), where they are part of the sialic acid-rich, cell-surface coats. A colloidal iron-stainable, cell-coat material is particularly concentrated on the epithelium. Accordingly, it has been repeatedly suggested (1, 2, 4-7) that this "epithelial polyanion" is responsible for establishing the charge-selective properties of the glomerular filter, and, concomitantly, that its loss leads to proteinuria since loss of epithelial cell-coat staining occurs in several renal diseases (1, 2, 5). Materials. Ruthenium red was purchased from Ventron Corp. (Danvers, MA); horse-spleen ferritin (2X crystallized, cadmium free) from Calbiochem; and chondroitin sulfates (types A, B, and C) and heparin (grade I) from Sigma. Chondroitinase ABC (Proteus vulgaris) was obtained from Miles; testicular hyaluronidase from Sigma; leech hyaluronidase from Biotrics, Inc. (Boston, MA); neuraminidase (Clostridium perfringens, NEUA) from Worthington; collagenase form III (Cl. histolyticum) from Advance Biofactures (Lynbrook, NY); and Pronase (Streptomyces griseus, grade B) from Calbiochem. Crude heparinase and purified heparitinase (Flavobacterium heparinium) were the generous gift of Alfred Linker (17).* Neuraminidase and heparitinase were tested by the Azocoll assay (18) and were free of proteolytic activity. Cationized ferritin was prepared as described previously (16).Perfusion Experiments. The left kidney was exposed and perfused as described (16). Initially, the kidney was flush...

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“…More recently Shibata et al [47,48] demonstrated that the soluble supernatant obtained from trypsin-digested rat kidney homogenate has the capacity to stimulate the production of nephrotoxic antiserum in rabbits. Furthermore, Mohos and Skoza [40] recently reported that sialic acid is contained in the antigenic determinant of the nephritogenic antigen. These authors demonstrated that neuraminidase treatment of rat glomeruli greatly reduced the capacity of glomeruli to remove the .…”

Section: Introductionmentioning

confidence: 99%

The Production of Congenital Malformations Using Tissue Antisera. X. Effectiveness of Kidney Antigens Treated with Neuraminidase or Trypsin

Leung

Brent

1972

Pediatr Res

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ExtractRabbit antineuraminidase-treated rat kidney and rabbit antitrypsin-treated rat kidney supernatant antisera were embryotoxic resulting in embryonic growth retardation, malformations, and death when injected into 15 pregnant rats. The same two antisera were also found to be nephrotoxic as manifested by their ability to induce proteinuria in 28 male rats. However, the antiserum against neuraminidasetreated rat kidney homogenate was significantly less nephrotoxic (averaging 46 mg urinary protein/24 hr) than the antiserum against the soluble supernatant obtained from trypsin-digested rat kidney homogenate (averaging 180 mg urinary protein/24 hr). The embryotoxic potency of these two antisera did not seem to correlate with their respective nephrotoxic potency. The less nephrotoxic antiserum, namely the antiserum against neuraminidase-treated rat kidney, is about five times as embryotoxic as that of the more nephrotoxic antiserum.Fluorescent-labeled antibody localization studies showed that the teratogenic antibodies localized in vivo in the maternal glomerular basement membrane, Reichert's membrane, and the endodermal cells of the visceral yolk sac of the developing embryo. There were at least two bands of identity between antiserum against trypsin-treated kidney supernatant and antiserum against neuraminidase-treated kidney homogenate.The possible role played by Reichert's membrane and the visceral yolk sac endodermal cells in teratogenesis induced by heterologous antibodies is discussed along with other relevant hypotheses. Speculation

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Glomerular Sialoprotein

Cited by 124 publications

References 21 publications

Anionic sites in the glomerular basement membrane. In vivo and in vitro localization to the laminae rarae by cationic probes.

Anionic sites in the glomerular basement membrane. In vivo and in vitro localization to the laminae rarae by cationic probes.

Presence of heparan sulfate in the glomerular basement membrane

The Production of Congenital Malformations Using Tissue Antisera. X. Effectiveness of Kidney Antigens Treated with Neuraminidase or Trypsin

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