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K J Assmann

Publications and source records attributed to K J Assmann.

At least 91 records · Page 5Linked to original sources
PubMed1990

Anti-GBM nephritis in the mouse: role of granulocytes in the heterologous phase.

The role of polymorphonuclear granulocytes (PMNs) was studied in a model of anti-GBM nephritis in mice, in which PMN depletion was induced by total body irradiation of 7.5 Gy. Both in complement-normal B10.D2 new and in C5-deficient B10.D2 old mice, PMN depletion completely prevented the albuminuria occurring after injection of low doses of anti-GBM serum, and severely depressed the albuminuria after injection of high doses. In immunofluorescence, glomerular deposition of antibody and C3 was similar to that in control mice. The glomerular influx of PMNs in both the complement-normal and C5-deficient controls was inhibited to 10% or less of control values. Fibrin deposition or necrosis did not occur. Injection of F(ab')2 fragments of the anti-GBM antibody in non-irradiated mice caused only limited PMN influx and reduced the albuminuria to physiological levels, although the binding of 125I labeled F(ab')2 fragments to the glomeruli was as high as 82% of that of the complete antibody. We conclude that the albuminuria in this model is Fc-dependent and largely, if not completely, dependent on the influx of PMNs in the glomeruli. Among the many experimental models of anti-GBM nephritis, this is the first one in which the heterologous phase is complement-independent but PMN-dependent.

Animals↗
PubMed1989

Diagnosis of renal allograft rejection by macrophage immunostaining with a CD14 monoclonal antibody, WT14.

Since acute interstitial rejection (AIR) of renal allografts is accompanied by an increase of macrophages in the graft the diagnostic value of immunohistological staining of biopsy specimens with WT14, a new monoclonal antibody of the CD14 cluster directed against monocytes/macrophages, with increased affinity for activated cells, has been tested retrospectively. With an indirect immunoperoxidase technique on frozen sections a diffuse interstitial increase of WT14-positive cells was seen, with a characteristic peritubular pattern, in all 44 patients with clinically and histologically proven AIR. This pattern was not seen in normal kidneys (n = 10), or in biopsy specimens from patients with proven cyclosporin nephrotoxicity (n = 9), chronic vascular rejection (n = 13), or various other renal diseases (n = 60). Comparative staining with other monoclonal antibodies against monocytes/macrophages showed a variable, mostly weak or less specific staining pattern than did WT14. The increased staining with WT14 proved to be a better indicator of AIR than increased HLA-DR staining on tubular epithelial cells.

Antibodies, Monoclonal↗
PubMed1989

[Deposition of light chains in various organs; light chain deposition disease].

The case is reported of a patient with renal insufficiency, proteinuria and heart failure caused by 'light chain deposition disease' (LCDD). A renal biopsy showed nodular glomerulosclerosis, IF examination revealed linear deposits of monoclonal lambda light chains along the glomerular and tubular basement membranes. Similar deposits could be shown in a skin biopsy. No light chains could be detected in urine and serum. The patient had a good response to treatment with melphalan and prednisone.

Acute Kidney Injury↗
PubMed1989

Antiglomerular basement membrane nephritis in beige mice. Deficiency of leukocytic neutral proteinases prevents the induction of albuminuria in the heterologous phase.

Antiglomerular basement membrane (GBM) nephritis with massive albuminuria can be induced in mice by injection of heterologous antibodies against mouse GBM. The albuminuria and the glomerular lesions in this model are not mediated by complement, but are dependent on the presence of polymorphonuclear granulocytes (PMN) in the glomeruli. Neutral serine proteinases and reactive oxygen metabolites produced by activated PMN have been implicated as agents contributing to tissue damage. We examined the role of leukocytic neutral proteinases by comparing the glomerular damage and albuminuria after injection of rabbit anti-mouse GBM antibodies in normal control mice (C57BL/6J, +/+) and in beige mice (C57BL/6J,bg/bg) in which PMN are deficient of the neutral proteinases elastase and cathepsin G. The dose-dependent albuminuria that occurred in control mice after injection of 1.4-22 mg of anti-GBM antibodies was not observed in beige mice, despite a comparable influx of PMNs in the glomeruli. By electron microscopy both strains showed a similar attachment of PMN to the denuded GBM together with swelling and necrosis of endothelial cells. Elastase activity of extracts from PMN of beige mice was only 10-15% of the activity of control mice. In vitro, GBM degradation by PMN extracts of beige mice was 70% lower than that seen in control experiments. PMNs of beige and control mice showed no differences in superoxide production. In addition, administration of scavengers of reactive oxygen metabolites, such as catalase and desferrioxamine, did not prevent the albuminuria in this model. These findings support the important contribution of leukocytic neutral proteinases to the induction of albuminuria in the acute phase of anti-GBM nephritis in the mouse.

Albuminuria↗
PubMed1989

The development of anti-glomerular basement membrane nephritis in two children with Alport's syndrome after renal transplantation: characterization of the antibody target.

Two children with Alport's syndrome are described, who developed anti-glomerular basement membrane (GMB) antibody-mediated nephritis after renal transplantation. The reactivity of antibodies in their serum with collagenase-solubilized normal GBM was examined by SDS-PAGE with one- and two-dimensional immunoblotting. The specificity was compared with that of antibodies present in serum from a patient with Goodpasture's syndrome, and a mouse monoclonal antibody (MCA-P1), directed against the Goodpasture antigen. All reacted in a similar way with collagenase-solubilized GBM. Since abnormalities in the composition of the GBM are present in Alport's syndrome, it is proposed that differing antigen composition of GBM in the host compared with the donor kidney, together with transplant rejection, may have provoked the development of post-transplant anti-GBM antibodies.

Adolescent↗
PubMed1989

A sporadic case of acute Hantavirus nephropathy in The Netherlands.

A 32-yr-old man presented with acute renal failure preceded by a viral-like disease with high fever, bilateral loin pain, nausea, headache and slight thrombocytopenia. Renal biopsy revealed only minor tubulointerstitial abnormalities. Renal function completely normalised within 10 days after hospitalisation. The diagnosis of acute Hantavirus nephropathy was proved by serological examinations.

Acute Kidney Injury↗
PubMed1989

Involvement of an antigen distinct from the Heymann antigen in membranous glomerulonephritis in the mouse.

Membranous glomerulonephritis in the mouse can be induced by injection of a heterologous antiserum against murine pronase digested renal tubular antigens (TApron). The antigenic target in the glomerular capillary wall is different from the Heymann antigen (gp 330). It shows the characteristics of a smaller antigen (gp 90) that can also be detected by a monoclonal antibody. We isolated the anti-gp 90 component from the polyclonal antiserum by absorptions and elutions using mouse liver as a substrate, which lacks gp 330 but does express gp 90. Immunoprecipitation of radiolabeled renal proximal tubular brush borders demonstrated that the mouse liver eluate reacted with gp 90 but not with gp 330. In immunofluorescence, the eluate bound to the glomerular capillary wall of both mouse and rat in a homogeneous pattern. Injection of the eluate led to a transient, homogeneous binding to the glomerular capillary wall of the mouse and also, although to a lesser extent, to that of the rat. Injection in mice presensitized against rabbit immunoglobulins caused a more permanent granular binding in a pattern typical of membranous glomerulonephritis. The results demonstrate that an antigen with a molecular weight and a kidney distribution different from the Heymann antigen can serve as target for antibody-mediated membraneous glomerulonephritis in the mouse. Furthermore, they suggest that this antigen may also be involved in the membranous glomerulonephritis of the rat in addition to the Heymann antigen.

Animals↗
PubMed1988

An improved sensitive and simple microassay of mouse complement.

A simple and fast hemolytic microassay was developed for the determination of classical pathway complement activity in mouse serum. The assay is based on hemolysis of sheep red blood cells (SRBC) that are sensitized with polyclonal mouse antibodies. The degree of hemolysis was measured in the reaction supernatants by photometric reading in an ELISA plate scanner at 405 nm wavelength. It was found that some batches of unpurified mouse anti-SRBC antibodies gave insufficient hemolysis. Analysis of two antibody preparations indicated that this might be caused by anti-complementary factors in the ascites fluid, and by an excess of non-complement fixing IgG1 antibodies. For optimal and standardized results, removal of anticomplementary factors and enrichment for complement fixing IgG2 antibodies was required and was achieved using protein A purified anti-SRBC IgG. In our assay it is possible to determine CH50 titers in triplicate in 80 microliters samples of individual mouse sera with high sensitivity. Using this rapid one-step method large numbers of tests could be performed in 1 day.

Animals↗
PubMed1988

Antiglomerular basement membrane nephritis in the mouse. Study on the role of complement in the heterologous phase.

The role of complement was examined in a model of antiglomerular basement membrane nephritis in the mouse, induced by intravenous injection of goat anti-mouse glomerular basement membrane serum, and characterized by early glomerular lesions and a dose-dependent albuminuria. We compared the reaction after injection of the antiserum in complement-normal B10.D2 new mice with that in congenic, congenitally C5-deficient B10.D2 old mice, and in both strains after C3 depletion by treatment with cobra venom factor. The dose-dependent albuminuria was not affected by the absence of complement activation. Also, deficiency of C3 and/or C5 had no inhibitory effect on the histologic glomerular lesions: it did not reduce the influx of polymorphonuclear granulocytes in the glomerular capillary vessels, nor prevented the eventual intravascular coagulation. We conclude that complement-independent mechanisms are involved in the development of the heterologous phase of antiglomerular basement membrane nephritis in the mouse.

Albuminuria↗
PubMed1986

The organ distribution of gp-330 (Heymann antigen) and gp-90 in the mouse and the rat.

The Heymann antigen (gp-330) and an antigen with lower molecular weight (gp-90) are major constituents of the brush border of the renal proximal tubules in the rat and the mouse. The Heymann antigen can also be found at discrete sites in the glomerular visceral epithelium of the rat, but not of the mouse. Gp-90 is present diffusely along the glomerular capillary wall of rat and mouse. The Heymann antigen is probably the target antigen for membranous glomerulonephritis in the rat, while in the mouse, where this form of glomerulonephritis can also be induced, gp-90 seems to be the antigen involved. We have separated the antibody populations against these two antigens by preparing eluates from kidneys of rats and livers of mice that had been injected with an antiserum against pronase-digested mouse renal tubular antigens. Using these purified antibodies we have examined by indirect immunofluorescence the distribution of the two antigens on normal mouse and rat tissues. The expression of the Heymann antigen is limited to the epithelia of several organs, while gp-90 has a more widespread distribution in many cells of different origin and function in both the mouse and the rat.

Animals↗
PubMed1986

Effects of cyclosporin A on autoimmune disease in MRL/1 and BXSB mice.

MRL/1 and BXSB mice were treated daily with cyclosporin A (CyA) in an oral dose of 25 mg/kg body weight. With this dose, blood levels within the therapeutic range were obtained. In normal mice CyA in this dose significantly prolonged the survival of an H-2 incompatible skin graft, and suppressed delayed-type hypersensitivity (DTH). It had no influence on the magnitude of a primary antibody response. Autoimmune mice were treated from 6 to 22 weeks of age. CyA treatment did not alter significantly the anti-DNA and anti-IgG autoantibody levels in either strain compared with control mice, who received olive oil. There was a slight but significant increase in serum IgG levels in CyA-treated MRL/1 mice. Clinical signs of glomerulonephritis (decreased kidney function and albuminuria), and glomerular proliferation were not altered by CyA treatment in either strain. The amount of mesangial IgG deposits was reduced in CyA-treated MRL/1 mice, and remained unchanged in BXSB mice. The extent of the interstitial and perivascular infiltrates and the frequency and severity of necrotizing arteritis in the kidneys of MRL/1 mice were reduced by CyA treatment. The most prominent effect of CyA was an evident reduction in lymphoproliferation in MRL/1 mice. Mortality was not reduced by CyA treatment in MRL/1 and BXSB mice.

Animals↗
PubMed1985

Anti-GBM nephritis in the mouse: severe proteinuria in the heterologous phase.

Highly reproducible anti glomerular basement membrane (GBM) nephritis has been induced in the mouse after a single injection of rabbit or goat antibody against purified homologous GBM. The severity of albuminuria was closely related to the amount of antibody given. With doses of 4 mg or more, low serum albumin concentrations, sometimes accompanied by ascites and oedema, were observed after 1 week. Glomerular injury was characterized by an initial accumulation of polymorphonuclear granulocytes followed by thrombosis and necrosis, the extent of which defined the outcome of the glomerulonephritis. With high doses of antibody the exudative lesions entered a chronic phase, while at doses lower than 2 mg remission of the lesions occurred. Immunofluorescence studies showed prompt linear fixation of the injected antibodies to the glomerular capillary wall, accompanied by immediate binding of C3 in a fine granular pattern. Fibrin deposits appeared at 2 h in some glomeruli, increased thereafter, and were present after one day in more than 90% of the glomeruli in mice that had received 4 mg of antibody. This new reproducible model in the mouse is suited for the study of the relationship between activation of mediator systems, histological lesions, and proteinuria.

Animals↗
PubMed1985

Comparison of antigenic targets involved in antibody-mediated membranous glomerulonephritis in the mouse and rat.

Membranous glomerulonephritis in the mouse can be induced by a single injection of an antiserum against homologous, pronase-digested, renal tubular antigens (TAPron). In indirect immunofluorescence studies on normal mouse and rat kidneys it has now been found that the antiserum reacts strongly with the visceral epithelia of the mouse in a homogeneous pattern, while a faint granular staining is seen in the rat glomerulus against a homogeneous background. After injection in rats, a classic passive Heymann nephritis could be induced. By immunoprecipitation of radiolabeled rat renal brush borders (BB) it could be shown that anti-TAPron antisera contain antibodies to 330-kd and 90-kd BB proteins expressed by rat glomeruli. With the use of two monoclonal antibodies specific for the 330- and 90-kd proteins the homogeneous binding observed in rat and mouse glomeruli could be related to the 90-kd antigen, whereas the coarse irregular staining observed in rat glomeruli was only related to the 330-kd antigen. Immunoglobulins eluted from glomeruli of rats bound to rat glomeruli and reacted only with the 330-kd protein. They did not bind to mouse glomeruli. Discrete localization in coated pits, multivesicular bodies, and endoplasmic reticulum of the visceral epithelia was seen in immunoelectron-microscopy. The results presented thus demonstrate that immune deposits induced in the rat by anti-TAPron antibodies are related to antibodies specific for the 330-kd antigen, ie, the classic Heymann antigen. By contrast, immune deposits observed in the mouse are related to antibodies specific for a 90-kd protein.

Animals↗
PubMed1983

Membranous glomerulonephritis in the mouse.

Glomerulonephritis was induced in C57. B110 mice by a single injection of rabbit IgG against homologous, pronase-digested, renal tubular antigens. The heterologous phase was characterized by a transient increase of glomerular permeability with fixation of rabbit IgG to the capillary walls, in a linear or fine-granular pattern, and to the brush borders of the proximal tubuli. The autologous phase was marked by the immune response to the injected protein, during which subepithelial immune deposits, consisting of mouse IgG1, rabbit IgG, and mouse C3 developed. Small amounts were still present at 1 year after the injection of antiserum. The antibody response of the mice correlated with the development and resolution of the deposits. None of the mice developed a nephrotic syndrome. Control mice treated with normal rabbit IgG did not show immune deposits in their kidneys at any stage despite a comparable antibody response to rabbit IgG. Immunoelectronmicroscopy showed that the rabbit antibodies fixed directly to an antigen in the cell membrane of the glomerular visceral epithelium. It seems, therefore, likely that in situ formation of subepithelial immune complexes occurred in the autologous phase by fixation of mouse immunoglobulins to rabbit IgG already present in the glomerular wall.

Animals↗