Immune complex-induced defects in glomerular basement membrane charge can be “repaired” despite continuing glomerular disease

1987 ◽  
Vol 153 (2) ◽  
pp. 189-193 ◽  
Author(s):  
Peter N. Furness ◽  
David R. Turner
Keyword(s):  
Basement Membrane ◽  
Immune Complex ◽  
Glomerular Basement Membrane ◽  
Glomerular Disease ◽  
Membrane Charge ◽  
Induced Defects

scholarly journals Interaction of cationized antigen with rat glomerular basement membrane: In situ immune complex formation

1982 ◽  
Vol 22 (1) ◽  
pp. 27-35 ◽  
Author(s):  
Arnold Vogt ◽  
Rolf Rohrbach ◽  
Fujio Shimizu ◽  
Haruo Takamiya ◽  
Stephen Batsford
Keyword(s):  
Complex Formation ◽  
Basement Membrane ◽  
Immune Complex ◽  
Glomerular Basement Membrane ◽  
Immune Complex Formation

The molecular basis of glomerular basement membrane disorders

2018 ◽  
Author(s):  
Rachel Lennon ◽  
Neil Turner
Keyword(s):  
Extracellular Matrix ◽  
Basement Membrane ◽  
Glomerular Basement Membrane ◽  
Heparan Sulphate ◽  
Collagen Iv ◽  
Basement Membranes ◽  
Glomerular Disease ◽  
The Body ◽  
Monogenic Disorders ◽  
Filtration Barrier

The glomerular basement membrane (GBM) is a condensed network of extracellular matrix molecules which provides a scaffold and niche to support the function of the overlying glomerular cells. Within the glomerulus, the GBM separates the fenestrated endothelial cells, which line capillary walls from the epithelial cells or podocytes, which cover the outer aspect of the capillaries. In common with basement membranes throughout the body, the GBM contains core components including collagen IV, laminins, nidogens, and heparan sulphate proteoglycans. However, specific isoforms of these proteins are required to maintain the integrity of the glomerular filtration barrier.Across the spectrum of glomerular disease there is alteration in glomerular extracellular matrix (ECM) and a number of histological patterns are recognized. The GBM can be thickened, expanded, split, and irregular; the mesangial matrix may be expanded and glomerulosclerosis represents a widespread accumulation of ECM proteins associated with loss of glomerular function. Whilst histological patterns may follow a sequence or provide diagnostic clues, there remains limited understanding about the mechanisms of ECM regulation and how this tight control is lost in glomerular disease. Monogenic disorders of the GBM including Alport and Pierson syndromes have highlighted the importance of both collagen IV and laminin isoforms and these observations provide important insights into mechanisms of glomerular disease.

scholarly journals Histones have high affinity for the glomerular basement membrane. Relevance for immune complex formation in lupus nephritis.

1989 ◽  
Vol 169 (6) ◽  
pp. 1879-1894 ◽  
Author(s):  
T M Schmiedeke ◽  
F W Stöckl ◽  
R Weber ◽  
Y Sugisaki ◽  
S R Batsford ◽  
...  
Keyword(s):  
Complex Formation ◽  
Lupus Nephritis ◽  
Basement Membrane ◽  
Immune Complex ◽  
Glomerular Basement Membrane ◽  
Isolated Glomeruli ◽  
Immune Complex Glomerulonephritis ◽  
High Affinity ◽  
Peritubular Capillaries ◽  
Immune Complex Formation

An effort has been made to integrate insights on charge-based interactions in immune complex glomerulonephritis with nuclear antigen involvement in lupus nephritis. Attention was focussed on the histones, a group of highly cationic nuclear constituents, which could be expected to bind to fixed anionic sites present in the glomerular basement membrane (GBM). We demonstrated that all histone subfractions, prepared according to Johns (4), have a high affinity for GBM and the basement membrane of peritubular capillaries. Tissue uptake of 125I-labeled histones was measured by injecting 200 micrograms of each fraction into the left kidney via the aorta and measuring organ uptake after 15 min. In glomeruli isolated from the left kidneys, the following quantities of histones were found: f1, 13 micrograms; f2a (f2al + f2a2), 17 micrograms; f2b, 17 micrograms; and f3, 32 micrograms. Kinetic studies of glomerular binding showed that f1 disappeared much more rapidly than f2a. The high affinity of histones (pI between 10.5 and 11.0; mol wt 10,000-22,000) for the GBM correlates well with their ability to form aggregates (mol wt greater than 100,000) for comparison lysozyme (pI 11, mol wt 14,000), which does not aggregate spontaneously bound poorly (0.4 micrograms in isolated glomeruli). The quantity of histones and lysozyme found in the isolated glomeruli paralleled their in vitro affinity for a Heparin-Sepharose column (gradient elution studies). This gel matrix contains the sulfated, highly anionic polysaccharide heparin, which is similar to the negatively charged heparan sulfate present in the GBM. Lysozyme eluted with 0.15 M NaCl, f1 with 1 M NaCl, and f2a, f2b, and f3 could not be fully desorbed even with 2 M NaCl; 6 M guanidine-HCl was necessary. Two further findings of great relevance for the concept of induction of immune complex glomerulonephritis by histones were: (a) glomerular-bound histone was accessible for specific antibody given intravenously; and (b) prior binding of histones promoted glomerular deposition of anionic antigens, as could be shown with ssDNA fragments. These data justify the proposal that glomerular deposition of histones can induce immune complex formation, start an inflammatory process, and produce tissue damage.

scholarly journals Glomerular basement membrane and related glomerular disease

2012 ◽  
Vol 160 (4) ◽  
pp. 291-297 ◽  
Author(s):  
Ying Maggie Chen ◽  
Jeffrey H. Miner
Keyword(s):  
Basement Membrane ◽  
Glomerular Basement Membrane ◽  
Glomerular Disease

Basement membrane charge in human glomerular disease

1986 ◽  
Vol 150 (4) ◽  
pp. 267-278 ◽  
Author(s):  
Peter N. Furness ◽  
David R. Turner ◽  
Roger E. Cotton
Keyword(s):  
Basement Membrane ◽  
Glomerular Disease ◽  
Membrane Charge
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