scholarly journals Enhancement of glomerular immune complex deposition by a circulating polycation.

1984 ◽  
Vol 160 (1) ◽  
pp. 286-293 ◽  
Author(s):  
J L Barnes ◽  
M A Venkatachalam

It is known that polycations bind to and neutralize glomerular polyanions. Here we examine the effect of the polycation polyethyleneimine (PEI) on glomerular deposition of preformed immune complexes. Bovine serum albumin (BSA)-anti-BSA immune complexes made in 40 times antigen excess were administered following intravenous injection of PEI. Glomerular localization of immune deposits was assessed by quantitative immunofluorescence and electron microscopy and compared to controls receiving diluent without PEI followed by the same dose in immune complexes. In rats receiving PEI, deposits were localized within the glomerular basement membrane (GBM) of all peripheral capillary walls and in the mesangium. In controls, deposits localized exclusively within the mesangium in smaller amounts than after PEI. Thus, neutralization of glomerular polyanion by a circulating polycation enhances the deposition and alters the distribution of immune complexes in glomeruli.

1977 ◽  
Vol 14 (5) ◽  
pp. 482-489 ◽  
Author(s):  
J. R. Easley ◽  
W. H. Halliwell

Fifteen rabbits were injected with one dose of 250 milligrams per kilogram of bovine serum albumin intravenously to induce acute serum sickness. The kidneys were removed from groups of five rabbits each at 10, 12 and 14 days after injection and examined by light, electron and immunofluorescent microscopy for evidence of immune complex glomerulonephritis. Urine was examined for protein when rabbits died. Glomerulonephritis was found in eight rabbits by light microscopy and in 10 rabbits by electron microscopy. Only one rabbit had positive immunofluorescence for immunologic components and only two rabbits had proteinuria. Hypercellularity was the primary change seen by light microscopy. Ultrastructural changes were numerous and various, and the major changes recognized were irregularity of the glomerular basement membrane, increased mesangial matrix, hypercellularity, endothelial hypertrophy, mesangial deposits, epithelial foot process fusion and mesangial circumferential interposition. Subepithelial humps were seen in only four rabbits; none of these rabbits had proteinuria. We concluded that increased permeability followed the deposition of immune complexes and development of ultrastructural lesions.


2001 ◽  
Vol 125 (4) ◽  
pp. 534-536
Author(s):  
Sanjeev Sethi ◽  
Oyedele A. Adeyi ◽  
Helmut G. Rennke

Abstract We report a case of crescentic glomerulonephritis that presented with extensive crescent formation and fibrinoid necrosis in the glomeruli. Immunofluorescence staining was strongly positive for linear and pseudolinear staining of the capillary walls for immunoglobulin G (IgG) in the absence of significant mesangial staining. Histologic examination and immunofluorescence staining suggested a diagnosis of anti–glomerular basement membrane disease. However, electron microscopy showed the presence of numerous fibrillary deposits in the subepithelial areas of the glomerular capillary walls, supporting the diagnosis of fibrillary glomerulonephritis. Test results for circulating anti–glomerular basement membrane antibodies were negative. We report this interesting case to illustrate the point that fibrillary glomerulonephritis should be considered in the differential diagnosis of crescentic glomerulonephritis with linear and pseudolinear IgG deposits within the capillary walls. In such cases, electron microscopy is critical in differentiating the cause of crescentic glomerulonephritis.


Author(s):  
D. Marsh

As a result of vasectomy, spermatozoa are confined to the epididymis and vas deferens, where they degenerate, releasing antigens that enter the circulation or are engulfed by macrophages. Multiple antigens of the sperm can elicit production of autoantibodies; circulating anti-sperm antibodies are found in a large percentage of vasectomized men, indicating the immunogenicity of the sperm. The increased prevalence of macrophages in the liomen of the rhesus monkey testicular efferent ducts after vasectomy led to further study of this region. Frozen sections were used for evaluation of immunopathological status by fluorescence microscopy with fluorescein-conjugated antibody. Subsequent granular deposits of immune complexes were revealed by positive immunofluorescence staining for complement. The immune complex deposition in the basement membrane surrounding the efferent ducts implies that this region is involved in antigen leakage (Fig. 1).


1982 ◽  
Vol 93 (2) ◽  
pp. 489-494 ◽  
Author(s):  
Y S Kanwar ◽  
L J Rosenzweig

The negative charges of the sulfated glycosaminoglycans (GAGs) of the glomerular basement membrane (GBM) were differentially neutralized by perfusin with high molarity buffers in order to determine whether or not these charges protect the GBM from being clogged by circulating plasma macromolecules. Progressive elimination of the negative charges resulted in clogging of the GBM by perfused native ferritin (NF) and bovine serum albumin as evidenced ultrastructurally by the increase in accumulation of NF in the GBM. In addition, the permeability of the GBM to 125I-insulin, a macromolecule which is normally freely permeable, and the glomerular filtration rate (as determined by [3H]inulin clearance) were markedly reduced after the GBM had been clogged with NF in the presence of high molarity buffer, thereby indicating that clogging severely reduces the ability of the GMB to act as a selective filter. These findings are consistent with the idea that the sulfated GAGs of the GBM serve as anticlogging agents.


1986 ◽  
Vol 71 (5) ◽  
pp. 565-572 ◽  
Author(s):  
J. M. Boulton Jones ◽  
Lata Chandrachud ◽  
Hannah Mosely

1. Inherited differences in the quantity and site of renal deposition of antigen were studied in two inbred strains of healthy rats, one of which, Lewis, is susceptible to Heymann's nephritis and the other (DA) is resistant. 2. Deposition of human cationic immunoglobulin G (IgG) was significantly less in the liver, spleen and kidneys of Lewis rats compared with DA rats, which suggests that the density of the negatively charged molecules in the capillary walls of Lewis rats is less than in DA rats. Immunofluorescent studies of the kidneys 15 min after administration of cationic IgG showed that it could be detected only on the glomerular basement membrane (GBM) and that the intensity of the deposits was less in Lewis rats. 3. The mesangial uptake of aggregated IgG was greater in DA rats at all times studied. There was remarkable similarity in the glomerular processing of cationic IgG and aggregated IgG in both strains. 4. These differences in glomerular properties, capillary charge and mesangial uptake may lead to differences in the deposition of antigen within the glomerulus and in the response to the subsequent inflammatory reactions. This provides a new hypothesis for genetic predisposition of individuals to particular glomerulopathies.


2014 ◽  
Vol 306 (10) ◽  
pp. F1198-F1209 ◽  
Author(s):  
Jeffrey W. Pippin ◽  
Sean T. Glenn ◽  
Ronald D. Krofft ◽  
Michael E. Rusiniak ◽  
Charles E. Alpers ◽  
...  

Aging nephropathy is characterized by podocyte depletion accompanied by progressive glomerulosclerosis. Replacement of terminally differentiated podocytes by local stem/progenitor cells is likely a critical mechanism for their regeneration. Recent studies have shown that cells of renin lineage (CoRL), normally restricted to the kidney's extraglomerular compartment, might serve this role after an abrupt depletion in podocyte number. To determine the effects of aging on the CoRL reserve and if CoRL moved from an extra- to the intraglomerular compartment during aging, genetic cell fate mapping was performed in aging Ren1cCre × Rs-ZsGreen reporter mice. Podocyte number decreased and glomerular scarring increased with advanced age. CoRL number decreased in the juxtaglomerular compartment with age. There was a paradoxical increase in CoRL in the intraglomerular compartment at 52 and 64 wk of age, where a subset coexpressed the podocyte proteins nephrin, podocin, and synaptopodin. Transmission electron microscopy studies showed that a subset of labeled CoRL in the glomerulus displayed foot processes, which attached to the glomerular basement membrane. No CoRL in the glomerular compartment stained for renin. These results suggest that, despite a decrease in the reserve, a subpopulation of CoRL moves to the glomerulus after chronic podocyte depletion in aging nephropathy, where they acquire a podocyte-like phenotype. This suggests that they might serve as adult podocyte stem/progenitor cells under these conditions, albeit in insufficient numbers to fully replace podocytes depleted with age.


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