Anionic Binding Sites in the Glomerular Basement Membrane: Possible Role in the Pathogenesis of Immune Complex Glomerulonephritis

1980 ◽  
Vol 3 (1-6) ◽  
pp. 336-340 ◽  
Author(s):  
S. Batsford ◽  
T. Oite ◽  
H. Takamiya ◽  
A. Vogt
Keyword(s):  
Basement Membrane ◽  
Immune Complex ◽  
Glomerular Basement Membrane ◽  
Binding Sites ◽  
Immune Complex Glomerulonephritis ◽  
Anionic Binding Sites

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 Localization of the membrane attack complex (MAC) in experimental immune complex glomerulonephritis.

1983 ◽  
Vol 157 (6) ◽  
pp. 1885-1905 ◽  
Author(s):  
D Koffler ◽  
G Biesecker ◽  
B Noble ◽  
G A Andres ◽  
A Martinez-Hernandez
Keyword(s):  
Basement Membrane ◽  
Immune Complex ◽  
Immune Complexes ◽  
Tissue Injury ◽  
Membrane Attack Complex ◽  
Intense Staining ◽  
Immune Complex Glomerulonephritis ◽  
Filtration Barrier ◽  
Dense Deposits ◽  
Foot Process

The role of the membrane attack complex (MAC) as a mediator of renal tissue injury was evaluated in rats affected by bovine serum albumin (BSA)-induced immune complex glomerulonephritis. Immunofluorescence studies revealed concurrent deposits of IgG, BSA, C3, and the MAC along glomerular capillary walls, although the MAC manifested a more restricted distribution than that observed for immune complexes. Immunoelectron microscopic techniques were utilized to demonstrate immune complexes, C3, and the MAC within dense deposits in the subepithelial aspect of the basement membrane. Visceral epithelial foot processes were fused in areas overlying large dense deposits and exhibited intense staining for the MAC, lesser reactivity for C3 but IgG was absent from the foot process membranes. Smaller granular deposits of immune complexes, C3, and the MAC were observed in the subendothelial region of the lamina rara interna and the lamina densa. Immune complexes may activate the classical complement pathway causing diffuse injury to the glomerular basement membrane (GBM), allowing subepithelial accumulation of complexes. These observations implicate the MAC as a mediator of GBM and juxtaposed podocyte membrane injury, thereby contributing to disruption of the glomerular filtration barrier. IgG and C3 were demonstrated within tubulointerstitial regions on the surface of collagen fibers in close proximity to the tubular basement membrane (TBM) of proximal convoluted tubules. Within the TBM, C3 localization was prominent with diminished reactivity for the MAC, but IgG was not detectable. The demonstration of C3 and scant MAC deposits in the TBM of nonimmunized control rats without evidence of interstitial IgG and C3 deposits suggests that both nonimmune and immune processes play a role in the pathogenesis of extraglomerular lesions. Evidence derived from these morphologic studies indicates that the MAC is associated with injury to the GBM, foot process membranes of visceral epithelium, and the TBM. Further experiments designed to selectively enhance or inhibit the deposition of MAC and assess consequent renal dysfunction are required to substantiate hypotheses concerning the in vivo membranolytic potential of the MAC in experimental immune complex glomerulonephritis.

scholarly journals Concurrent Antiglomerular Basement Membrane Disease and Immune Complex Glomerulonephritis

Renal Failure ◽  
2006 ◽  
Vol 28 (1) ◽  
pp. 7-14 ◽  
Author(s):  
Zhao Cui ◽  
Ming-Hui Zhao ◽  
Su-Xia Wang ◽  
Gang Liu ◽  
Wan-Zhong Zou ◽  
...  
Keyword(s):  
Basement Membrane ◽  
Immune Complex ◽  
Immune Complex Glomerulonephritis

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
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