scholarly journals Loss of laminin epitopes during glomerular basement membrane assembly in developing mouse kidneys.

1992 ◽  
Vol 40 (12) ◽  
pp. 1943-1953 ◽  
Author(s):  
D R Abrahamson ◽  
P L St John
Keyword(s):  
Endothelial Cells ◽  
Basement Membrane ◽  
Horseradish Peroxidase ◽  
Glomerular Basement Membrane ◽  
Basement Membranes ◽  
Proteolytic Processing ◽  
Newborn Mouse ◽  
Capillary Loop ◽  
Loop Expansion ◽  
Initial Assembly

Kidney glomerular basement membranes (GMBs) originate in development from fusion of a dual basement membrane between endothelial cells and primitive epithelial podocytes. After fusion, segments of newly synthesized matrix, derived primarily from podocytes, appear as subepithelial outpockets and are spliced into GBMs during glomerular capillary loop expansion. To investigate GBM assembly further, we examined newborn mouse kidneys with monoclonal rat anti-mouse laminin IgGs (MAb) conjugated to horseradish peroxidase (HRP). In adults, these MAb strongly label glomerular mesangial matrices but bind only weakly or not at all to mature GBMs. In contrast, anti-laminin MAb intensely bound newborn mouse GBMs undergoing initial assembly. After intraperitoneal injection of MAb-HRP into neonates, dense binding occurred across both subendothelial and subepithelial pre-fusion GMBs as well as forming mesangial matrices. Considerably less MAb binding was seen, however, in post-fusion GBMs from more mature glomeruli in the same section, although mesangial matrices remained positive. In addition, new subepithelial segments in areas of splicing were negative. These results conflict with those obtained previously with injections of polyclonal anti-laminin IgGs into newborns or adults, which result in complete labeling of all GBMs. Although epitope masking cannot be completely excluded, we believe that decreased MAb binding to developing GBM reflects actual epitope loss. This loss could occur by laminin isoform substitution, conformational change, and/or proteolytic processing during GBM assembly.

scholarly journals SARS-CoV-2 infection and recurrence of anti-glomerular basement disease: a case report

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Alexander Winkler ◽  
Emanuel Zitt ◽  
Hannelore Sprenger-Mähr ◽  
Afschin Soleiman ◽  
Manfred Cejna ◽  
...  
Keyword(s):  
Basement Membrane ◽  
Glomerular Basement Membrane ◽  
Plasma Cells ◽  
Rapidly Progressive Glomerulonephritis ◽  
Kidney Injury ◽  
Pulmonary Involvement ◽  
Pulmonary Haemorrhage ◽  
Basement Membranes ◽  
High Avidity ◽  
History Of

Abstract Background Anti-glomerular basement membrane disease (GBM) disease is a rare autoimmune disease causing rapidly progressive glomerulonephritis and pulmonary haemorrhage. Recently, an association between COVID-19 and anti-glomerular basement membrane (anti-GBM) disease has been proposed. We report on a patient with recurrence of anti-GBM disease after SARS-CoV-2 infection. Case presentation The 31-year-old woman had a past medical history of anti-GBM disease, first diagnosed 11 years ago, and a first relapse 5 years ago. She was admitted with severe dyspnoea, haemoptysis, pulmonary infiltrates and acute on chronic kidney injury. A SARS-CoV-2 PCR was positive with a high cycle threshold. Anti-GBM autoantibodies were undetectable. A kidney biopsy revealed necrotising crescentic glomerulonephritis with linear deposits of IgG, IgM and C3 along the glomerular basement membrane, confirming a recurrence of anti-GBM disease. She was treated with steroids, plasma exchange and two doses of rituximab. Pulmonary disease resolved, but the patient remained dialysis-dependent. We propose that pulmonary involvement of COVID-19 caused exposure of alveolar basement membranes leading to the production of high avidity autoantibodies by long-lived plasma cells, resulting in severe pulmonary renal syndrome. Conclusion Our case supports the assumption of a possible association between COVID-19 and anti-GBM disease.

In vivo biosynthesis and turnover of glomerular basement membrane in diabetic rats

1982 ◽  
Vol 242 (4) ◽  
pp. F385-F389
Author(s):  
M. P. Cohen ◽  
M. L. Surma ◽  
V. Y. Wu
Keyword(s):  
Basement Membrane ◽  
Glomerular Basement Membrane ◽  
Diabetic Rats ◽  
Basement Membranes ◽  
Membrane Turnover ◽  
Proline Incorporation ◽  
Basement Membrane Collagen ◽  
Osmotic Lysis ◽  
Specific Activities

Glomerular basement membrane (GBM) was labeled in vivo by the injection of tracer amounts of tritiated proline into normal and streptozotocin-diabetic rats. Basement membrane biosynthesis and turnover were determined from the specific activities of proline and hydroxyproline in samples purified following osmotic lysis of glomeruli isolated 4 h to 12 days after injection. Peak radiolabeling of normal and diabetic GBM occurred within 24-48 h and 48-72 h, respectively, and, when corrected for differences in the serum proline specific activities, [3H]proline incorporation was greater in diabetic than in normal samples. In contrast to the subsequent time-dependent progressive decline in radiolabeling in basement membranes from normal animals, specific activities of proline and hydroxyproline in diabetic glomerular basement membrane did not change significantly over the same period of observation. Renal cortical mass and glomerular basement membrane collagen content were preserved in diabetic animals despite loss of body weight. The findings are compatible with prolongation of glomerular basement membrane turnover in experimental diabetes, and suggest that diminished degradation contributes to the accumulation of glomerular basement membrane that is characteristic of chronic diabetes.

scholarly journals Anionic charge concentration of rat kidney glomeruli and glomerular basement membrane

1993 ◽  
Vol 289 (3) ◽  
pp. 647-652 ◽  
Author(s):  
W D Comper ◽  
A S N Lee ◽  
M Tay ◽  
Y Adal
Keyword(s):  
Basement Membrane ◽  
Glomerular Basement Membrane ◽  
Electrostatic Interactions ◽  
Enzyme Inhibitors ◽  
Rat Kidney ◽  
Basement Membranes ◽  
Sulphate Content ◽  
Anionic Charge ◽  
Charge Concentration ◽  
A Charge

Estimates of levels of glomerular and glomerular-basement-membrane anion charge should serve as useful quantitative markers for the integrity of the tissues in health and disease. We have developed a simple, rapid, technique to measure this charge through the use of ion exchange with radioisotopes 22Na+ and 36Cl- at low ionic strengths in phosphate buffer. When this technique is used, normal glomeruli isolated from rat have a measured net anion charge concentration of 17.4 +/- 3.7 p-equiv. per glomerulus (n = 20). Perfused rat kidneys that lose approximately half of their glomerular heparan [35S]sulphate content (owing to oxygen-radical damage) exhibited a lower anion charge, of 7.5 +/- 1.6 p-equiv. per glomerulus (n = 5). Glomerular basement membranes prepared from rat glomeruli by a sonication-centrifugation procedure in the presence of enzyme inhibitors had a charge concentration of 6.3 +/- 0.7 mu-equiv./g wet wt. of tissue (n = 4), whereas membranes prepared by sonication, centrifugation, DNAse and detergent treatment had a charge concentration of 7.1 +/- 1.6 mu-equiv./g wet wt. (n = 4). Isotope-dilution experiments with 3H2O on these detergent-prepared glomerular basement membranes demonstrated that they had a water content of approx. 93%, which would then give a net anion charge concentration of 7.6 +/- 1.7 m-equiv./l (n = 4). These values are in good agreement with those obtained by others using titration techniques [Bray and Robinson (1984) Kidney Int. 25, 527-533]. The relatively low magnitude of glomerular anion charge in normal kidneys is consistent with other recent findings that glomerular anion charge is too low to affect the glomerular transport of charged molecules in a direct, passive, biophysical manner through electrostatic interactions.

The relation between connective tissue cells and intercellular substances, including basement membranes

1975 ◽  
Vol 271 (912) ◽  
pp. 363-377 ◽  
Keyword(s):  
Endothelial Cells ◽  
Basement Membrane ◽  
Immune Complexes ◽  
Hydrolytic Enzymes ◽  
Inflammatory Cells ◽  
Cell Types ◽  
Cellular Level ◽  
Basement Membranes ◽  
The Body ◽  
Pathological Changes

Basement membranes are distributed widely in the body forming an extracellular matrix for epithelial and endothelial cells. The collagenous and glycoprotein constituents of basement membranes are synthesized by these two cell types. Disturbance of the interactions between basement membranes and their associated epithelial and endothelial cells can lead to the pathological changes seen in diseases involving basement membranes. These changes are illustrated here by reference to glomerulonephritis induced by the deposition of immune complexes in the glomerulus of the kidney, and chronic inflammatory changes occurring in the lung after inhalation of asbestos. In these diseases basement membrane changes can occur in several ways. Hydrolytic enzymes released from inflammatory cells degrade basement membranes while other factors released from these cells may stimulate synthesis of basement membrane constituents by epithelial and endothelial cells. Alternatively the physical separation of epithelial and endothelial cells from their basement membranes by space-occupying substances such as immune complexes can interfere with feedback mechanisms leading to synthesis of basement membrane constituents and cell proliferation. Studies of these pathological changes at a cellular level should shed new light on the ways in which cells interact with their pericellular environment.

scholarly journals Glomerular basement membrane proteoglycans are derived from a large precursor.

1988 ◽  
Vol 106 (3) ◽  
pp. 963-970 ◽  
Author(s):  
D J Klein ◽  
D M Brown ◽  
T R Oegema ◽  
P E Brenchley ◽  
J C Anderson ◽  
...  
Keyword(s):  
Basement Membrane ◽  
Heparan Sulfate ◽  
Glomerular Basement Membrane ◽  
Core Protein ◽  
Proteolytic Processing ◽  
Precursor Protein ◽  
Immunological Methods ◽  
Core Proteins ◽  
Single Precursor ◽  
Species Being

The basement membrane heparan sulfate proteoglycan produced by the Englebreth-Holm-Swarm (EHS) tumor and by glomeruli were compared by immunological methods. Antibodies to the EHS proteoglycan immunoprecipitated a single precursor protein (Mr = 400,000) from [35S]methionine-pulsed glomeruli, the same size produced by EHS cells. These antibodies detected both heparan sulfate proteoglycans and glycoproteins in extracts of unlabeled glomeruli and glomerular basement membrane. The proteoglycans contained core proteins of varying size (Mr = 150,000 to 400,000) with a Mr = 250,000 species being predominant. The glycoproteins are fragments of the core protein which lack heparan sulfate side chains. Antibodies to glomerular basement membrane proteoglycan immunoprecipitated the precursor protein (Mr = 400,000) synthesized by EHS cells and also reacted with most of the proteolytic fragments of the EHS proteoglycan. This antibody did not, however, react with the P44 fragment, a peptide situated at one end of the EHS proteoglycan core protein. These data suggest that the glomerular basement membrane proteoglycan is synthesized from a large precursor protein which undergoes specific proteolytic processing.

Glomerular Endothelium and its Impact on Glomerular Filtration Barrier in Diabetes: Are the Gaps Still Illusive?

2018 ◽  
Vol 25 (13) ◽  
pp. 1525-1529 ◽  
Author(s):  
Joseph Fomusi Ndisang
Keyword(s):  
Endothelial Cells ◽  
Basement Membrane ◽  
Glomerular Filtration ◽  
Glomerular Basement Membrane ◽  
Healthy Individuals ◽  
Kidney Dysfunction ◽  
Glomerular Filtration Barrier ◽  
Filtration Barrier ◽  
Glomerular Endothelial Cells ◽  
Fenestrated Endothelium

Background: Glomerular capillaries are lined with highly specialized fenestrated endothelium which are primarily responsible to regulate high flux filtration of fluid and small solutes. During filtration, plasma passes through the fenestrated endothelium and basement membrane before it reaches the slit diaphragm, a specialized type of intercellular junction that connects neighbouring podocytes. Methods: A PubMed search was done for recent articles on components of the glomerular filtration barrier such as glomerular endothelial cells, podocytes and glomerular basement membrane, and the effect of diabetes on these structures. Results and Conclusion: Generally, the onset of kidney dysfunction in many diabetic patients is characterized by albuminuria/proteinuria, a pathophysiological event triggered by several factors including; (i) endothelial activation and shading of glycocalyx, (ii) loss of endothelial cell function, (ii) re-uptake of albumin by podocyte through a scavenger receptors and (iv) rearrangement of podocyte cytoskeleton. Howeover, as podocyte effacement does not always lead to proteinuria, the dynamic interplay between all constituents of the glomerular filtration barrier including podocytes, endothelial cells and the basement membrane may be fundamental for the effective filtration in healthy individuals. Thus, a putative cross-talk amongst podocytes, endothelial cells and the basement membrane in the homeostasis of glomerular function is envisaged. Although, the exact nature of this cross-talk remains to be clearly elucidated, it is possible that the interaction between: (i) glomerular endothelial cells and podocytes, (ii) glomerular endothelial cells and glomerular basement membrane, (iii) podocytes and glomerular basement membrane, and (iv) the simultaneous interaction amongst the three components collectively underpin effective filtration in healthy individuals. A comprehensive understanding of these different interactions still remains elusive. The elucidation of these multifaceted interactions will set the stage for greater understanding of the pathophysiology of kidney dysfunction.

scholarly journals Neutrophils adherent to a nonphagocytosable surface (glomerular basement membrane) produce oxidants only at the site of attachment

Blood ◽  
1985 ◽  
Vol 66 (1) ◽  
pp. 161-166 ◽  
Author(s):  
MC Vissers ◽  
WA Day ◽  
CC Winterbourn
Keyword(s):  
Superoxide Dismutase ◽  
Plasma Membrane ◽  
Cytochrome C ◽  
Basement Membrane ◽  
Horseradish Peroxidase ◽  
Cell Surface ◽  
Oxygen Uptake ◽  
Glomerular Basement Membrane ◽  
Cerium Chloride ◽  
Cytochrome C Reduction

Abstract Adherence of neutrophils to glomerular basement membrane containing immunoglobulin G aggregates was accompanied by a marked increase in oxygen uptake (eightfold). Very little of the O2 consumed was recovered as superoxide, measured by cytochrome c reduction, or as H2O2, measured with horseradish peroxidase and scopoletin. When neutrophils were incubated with the basement membrane preparation in the presence of cerium chloride to detect H2O2, electron micrographs showed cerium perhydroxide deposits in the contact area between the cells and the basement membrane, but not on the remainder of the cell surface. The results imply that superoxide is produced only where the plasma membrane is in contact with the basement membrane matrix, and that it mostly breaks down to H2O2 or undergoes other reactions at this site. The longer lifetime of H2O2 compared with that of superoxide allows some of the H2O2 produced to be detected in the medium. The results also suggest that the area of contact between the neutrophil and surfaces such as basement membrane is inaccessible to proteins in the medium, eg, cytochrome c. Circulating scavengers such as superoxide dismutase or catalase, or proteolytic inhibitors, may therefore be unable to control events occurring at this site.

scholarly journals TRANSPORT OF GLOBIN BY THE RENAL GLOMERULUS

1964 ◽  
Vol 120 (6) ◽  
pp. 1129-1138 ◽  
Author(s):  
Max G. Menefee ◽  
C. Barber Mueller ◽  
Allen L. Bell ◽  
Joseph K. Myers
Keyword(s):  
Endothelial Cells ◽  
Electron Microscope ◽  
Basement Membrane ◽  
Basement Membranes ◽  
Renal Glomerulus ◽  
Thin Sections ◽  
Characteristic Appearance ◽  
Pass Through ◽  
Surrounding Membrane ◽  
Glomerular Capillaries

Purified human globin injected into rats forms aggregates which are identifiable by their characteristic appearance in thin sections in the electron microscope and by their positive autoradiographs when the globin is tritiated before injection. Globin is taken up by endothelial cells of glomerular capillaries and is transported across the cell within the limits of a surrounding membrane. Globin is rarely seen to pass through fenestrations. Globin is also taken into the stalk region where it is seen usually within the sponge fibers and only occasionally within stalk cells. Globin is seen in all stages of passage through the basement membranes and sponge fibers, which are not deformed by its passage. On the basis of the findings presented here and by others, it is postulated that the basement membrane and sponge fibers consist of a thixotrophic gel. After traversing the basement membrane, the globin passes between foot processes of the epithelial cells. The slit membranes are deformed by this passage and thus appear to be distinctive structures. The globin is next found free in Bowman's space; the earliest aggregates are seen there within 1 minute after injection. Globin taken up in the stalk region is slowly discharged and very little is found there 6 hours postinjection.

scholarly journals Mesangial cells organize the glomerular capillaries by adhering to the G domain of laminin α5 in the glomerular basement membrane

2003 ◽  
Vol 161 (1) ◽  
pp. 187-196 ◽  
Author(s):  
Yamato Kikkawa ◽  
Ismo Virtanen ◽  
Jeffrey H. Miner
Keyword(s):  
Cell Adhesion ◽  
Basement Membrane ◽  
Glomerular Basement Membrane ◽  
Mesangial Cell ◽  
Mesangial Cells ◽  
Basement Membranes ◽  
Domain Specific ◽  
Integrin Α3β1 ◽  
Glomerular Capillaries

In developing glomeruli, laminin α5 replaces laminin α1 in the glomerular basement membrane (GBM) at the capillary loop stage, a transition required for glomerulogenesis. To investigate domain-specific functions of laminin α5 during glomerulogenesis, we produced transgenic mice that express a chimeric laminin composed of laminin α5 domains VI through I fused to the human laminin α1 globular (G) domain, designated Mr51. Transgene-derived protein accumulated in many basement membranes, including the developing GBM. When bred onto the Lama5 −/− background, Mr51 supported GBM formation, preventing the breakdown that normally occurs in Lama5 −/− glomeruli. In addition, podocytes exhibited their typical arrangement in a single cell layer epithelium adjacent to the GBM, but convolution of glomerular capillaries did not occur. Instead, capillaries were distended and exhibited a ballooned appearance, a phenotype similar to that observed in the total absence of mesangial cells. However, here the phenotype could be attributed to the lack of mesangial cell adhesion to the GBM, suggesting that the G domain of laminin α5 is essential for this adhesion. Analysis of an additional chimeric transgene allowed us to narrow the region of the α5 G domain essential for mesangial cell adhesion to α5LG3-5. Finally, in vitro studies showed that integrin α3β1 and the Lutheran glycoprotein mediate adhesion of mesangial cells to laminin α5. Our results elucidate a mechanism whereby mesangial cells organize the glomerular capillaries by adhering to the G domain of laminin α5 in the GBM.

scholarly journals Neutrophils adherent to a nonphagocytosable surface (glomerular basement membrane) produce oxidants only at the site of attachment

Blood ◽  
1985 ◽  
Vol 66 (1) ◽  
pp. 161-166
Author(s):  
MC Vissers ◽  
WA Day ◽  
CC Winterbourn
Keyword(s):  
Superoxide Dismutase ◽  
Plasma Membrane ◽  
Cytochrome C ◽  
Basement Membrane ◽  
Horseradish Peroxidase ◽  
Cell Surface ◽  
Oxygen Uptake ◽  
Glomerular Basement Membrane ◽  
Cerium Chloride ◽  
Cytochrome C Reduction

Adherence of neutrophils to glomerular basement membrane containing immunoglobulin G aggregates was accompanied by a marked increase in oxygen uptake (eightfold). Very little of the O2 consumed was recovered as superoxide, measured by cytochrome c reduction, or as H2O2, measured with horseradish peroxidase and scopoletin. When neutrophils were incubated with the basement membrane preparation in the presence of cerium chloride to detect H2O2, electron micrographs showed cerium perhydroxide deposits in the contact area between the cells and the basement membrane, but not on the remainder of the cell surface. The results imply that superoxide is produced only where the plasma membrane is in contact with the basement membrane matrix, and that it mostly breaks down to H2O2 or undergoes other reactions at this site. The longer lifetime of H2O2 compared with that of superoxide allows some of the H2O2 produced to be detected in the medium. The results also suggest that the area of contact between the neutrophil and surfaces such as basement membrane is inaccessible to proteins in the medium, eg, cytochrome c. Circulating scavengers such as superoxide dismutase or catalase, or proteolytic inhibitors, may therefore be unable to control events occurring at this site.

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