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Biomedical subjects

P Verroust

Publications and source records attributed to P Verroust.

At least 73 records · Page 4Linked to original sources
PubMed1986

Polyvalent antigen-antibody interactions are required for the formation of electron-dense immune deposits in passive Heymann's nephritis.

In order to analyze the initial steps involved in the formation of subepithelial electron-dense immune deposits, the authors induced passive Heymann's nephritis in rats by intravenous injection of monoclonal or polyclonal antibodies to the relevant antigen, a 330,000-dalton brush border protein also expressed within coated pits of glomerular epithelial cells. Whereas both mono- and polyclonal antibodies induced deposits detectable by indirect immunofluorescence, electron-dense deposits were only found in glomerular capillary walls of rats injected with polyclonal antibodies. Immunoultrastructural analysis confirmed the subepithelial location of heterologous IgG: monoclonal antibodies were essentially confined to the coated pits of glomerular epithelial cells, whereas polyclonal antibodies were detected in coated pits and in the subepithelial electron-dense deposits. In the face of an excess of circulating antibody, gp 330 was not detectable in the deposits, but a striking increase in the number of endoplasmic reticula positive for gp 330 was found. The results indicate that highly cross-linked immune complexes formed by polyvalent antibodies on the epithelial cell surface are necessary for the induction of subepithelial electron-dense deposits.

Animals↗
PubMed1986

Ultrastructural localization by monoclonal antibodies of brush border antigens expressed by glomeruli. II. Extrarenal distribution.

An immunoultrastructural study has been undertaken for analysis of the extrarenal localization of two brush border (BB) glycoproteins of 90 kd and 330 kd expressed by glomeruli. In previous studies on renal tissue, it has been shown that gp 330 is restricted to coated pits and BB intermicrovillar invaginations, whereas gp 90 is diffusely distributed on epithelial cell membranes and in addition expressed on glomerular endothelial cells. At variance from observations made in the kidney, gp 330 and gp 90 are mainly expressed on different epithelial cell types: gp 330 is found on the coated pits of the epithelium lining the epididymis and on the entire surface of the microvilli of Type II pneumocytes, whereas gp 90 is detected on the gut brush border and the biliary pole of hepatocytes; gp 90 is also found on endothelia lining all distal capillary beds studied in heart, lung, liver, and spleen. These observations thus indicate that gp 90 is expressed by a wide variety of cell types, all associated with high membrane turnover. Conversely, gp 330 has a restricted distribution at the organ, cellular and subcellular level and may be related with a defined system of receptor-mediated endocytosis.

Animals↗
PubMed1986

Ultrastructural localization by monoclonal antibodies of brush border antigens expressed by glomeruli. I. Renal distribution.

The authors have previously reported the production of monoclonal anti-brush border antibodies defining two glycoprotein (gp) antigens of 90 and 330 kd which are also expressed on glomerular cells and may thus be of significance for in situ formation of immune complexes. The 330-kd antigen is involved in Heymann's nephritis, whereas the 90-kd antigen induces transient glomerular immune deposits. In this report, the authors describe the renal ultrastructural localization of the two antigens, which are both detectable on brush border and glomerular epithelial cells but assume contrasting patterns: gp 90 is diffusely present on the cell membranes, whereas gp 330 is concentrated in the intermicrovillar region and within the coated pits. Their localization within proximal tubular cells, on the membrane of intracytoplasmic vesicles, suggests that they are involved in endocytosis. In addition, gp 90 is expressed on endothelial cells lining glomerular capillaries. These observations may help us to understand the formation and different kinetics of immune glomerular deposits.

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↗
PubMed1984

A monoclonal antibody to brush border and passive Heymann nephritis.

An IgG2a monoclonal antibody (MoAb) reacting with the brush border of the renal proximal tubule and glomerular capillary wall was produced by fusion of NS1 myeloma cells with spleen cells from BALB/c mice immunized with renal brush border preparations from rat kidney cortex. This antibody reacts with a 90,000 mol. wt protein which can be isolated by immunoprecipitation of radiolabelled brush border or glomerular preparations and localized on these structures by immunoperoxidase electron microscopy, thus demonstrating the presence of common antigenic determinants. Survey of various organs showed that the MoAb reacted with the brush border of the gut, but also with antigens associated with the distal vascular system. In the liver antigenic determinants were located along the sinusoid walls but mainly on bile canaliculi. Specific glomerular binding could be demonstrated in vivo by immunofluorescence after an intravenous injection of 2 mg of antibody or by paired label methodology using tracer amounts. Kinetics however were dramatically different from those observed in classical passive Heymann nephritis since glomerular binding was transient during the first hours after injection. Binding was also found in tubular structures, as well as in lung, liver, spleen and heart. These results identify a well defined antigen-antibody system responsible for the formation of transient extramembranous glomerular deposits and may be relevant to some human cases of glomerulonephritis. They may also provide new models to study glomerular and tubular transfer of membrane bound antibodies.

Animals↗
PubMed1984

Production and characterization of monoclonal antibodies against rat brush border antigens of the proximal convoluted tubule.

In order to understand further the processes involved in immunological injury of the kidney, we have prepared monoclonal antibodies against brush border (BB) antigens of rat proximal tubule. The 27 antibodies which constitute the basis of this report have been cloned, characterized immunochemically, and classified in three specificity groups on the basis of tissue reactivity. The first group is made up of six antibodies reacting with antigens simultaneously present on BB and glomerulus: three are directed against a high molecular weight (MW) protein which migrates with an apparent MW of 330,000; two react with a 90,000 MW protein that is present diffusely on renal and intestinal BB as well as on endothelial cells; one recognizes an antigen exclusively present on superficial tubules and glomerular epithelial cells, which could not be chemically characterized. The second group is made up of eight antibodies present on renal and intestinal BB: five react with a 120,000 MW antigen, one with a 300,000 MW antigen. The third group comprises 13 antibodies. Two are directed against antigens present within the cytoplasm or the basolateral membranes of renal tubules. Eleven react with intracellular antigens probably related to the cytoskeleton. Since they have been identified through several fusions, some of the monoclonal antibodies described are probably directed against immunodominant proteins of the BB. They open new possibilities for purifying the corresponding antigens by affinity chromatography as well as for obtaining BB preparations selectively depleted of the strongest immunogens thus favouring antibody production to previously unrecognized antigens.

Animals↗
PubMed1984

Renal failure in myeloma: relationship with isoelectric point of immunoglobulin light chains.

Renal failure is a frequent but inconstant complication of myeloma related to light chain excretion. Since it has been suggested that cationic light chains (lc) are most likely to induce renal damage, we have studied the isoelectric point (pI) of light chains produced by 17 patients with myeloma and related the results to the type and severity of renal damage assessed clinically and pathologically. In order to do so, we have applied immunoenzymatic techniques which allow identification of light chain types as well as measurement of pI without prior purification. Ten of fifteen patients with renal failure produced lambda light chains. There was no simple relationship between the isoelectric point and nephrotoxicity. However, light chains with the lowest pI observed in this series were associated with normal renal function in two cases and with acute reversible but severe renal failure requiring dialysis in five cases. By contrast, pI values above 6.0 observed in the remaining patients were associated with moderate renal failure in six patients with recently diagnosed myeloma and with irreversible renal failure, and in two patients in whom myeloma had been evolutive for several years. We thus suggest that further pI measurements may help to identify light chains with different nephrotoxic potentials.

Acute Kidney Injury↗
PubMed1983

Glomerular and vascular IgG deposits in HgCl2 nephritis: role of circulating antibodies and of immune complexes.

The respective roles of circulating anti-glomerular basement membrane antibodies and of circulating immune complexes in the appearance of glomerular linear and granular IgG deposition during HgCl2-induced glomerulonephritis in the Brown-Norway rat has been studied. Syngeneic kidney transplantations have been performed at various phases of the disease. Results show that circulating antibodies are responsible for linear IgG deposition which did not change to granular deposits during the course of the disease. Electron-dense subepithelial deposits occurred only when circulating immune complexes were detected. These experiments strongly suggest that, in the mercury model, circulating immune complexes are responsible for granular IgG deposits observed in arteries and in the subepithelial space of glomeruli.

Animals↗
PubMed1983

Immunopathological studies of polyarteritis nodosa and Wegener's granulomatosis: a report of 43 patients with 51 renal biopsies.

Although it is generally considered that vasculitis of the polyarteritis nodosa (PAN) group and Wegener's granulomatosis (WG) is immune complex (IC) mediated, there are no simultaneous data on circulating IC, complement levels and deposits of Ig and complement in the kidney. Therefore we have performed a retrospective study of 43 patients suffering from PAN and WG. Ig glomerular deposits were uncommon and scanty, except in two patients with WG; C3 deposits were detected in 12 patients, whereas fibrinogen was constantly found when lesions were recent and active. Similar data were obtained for the renal vessel walls. Contrasting with these results, rheumatoid factors and cryoglobulins, suggestive of the presence of circulating IC, were detected respectively in nine of 39 and seven of 37 patients, and IC 'activity' assessed by the Raji cell assay and the Clq binding assay was found respectively in six of 17 and nine of 10 patients before treatment, and in none of 10 and five of seven patients in remission. Haemolytic complement activity and complement components were never decreased, but the C3d breakdown product of C3 was elevated in all the eight patients studied before treatment. Signs of persistent hepatitis B virus (HBV) infection were detected in five of 25 patients of the PAN group, whereas three of eight patients with WG had only anti-HBV antibodies. Furthermore, cytomegalovirus (CMV) could be isolated from the blood in a case of WG before the treatment was started. Persistent interferonaemia was detected in one of five patients. These results suggest either that renal deposition of CIC is transient, the paucity of Ig deposits being due to rapid clearance of IC by phagocytic cells; or alternatively that vascular and glomerular lesions are not caused by CIC, as in some cases of experimental vasculitis induced by infectious agents.

Adolescent↗
PubMed1983

Severe glomerular epithelial cell damage does not prevent passive Heyman nephritis in rats.

Passive Heymann nephritis (PHN) is an experimental model of membranous glomerulopathy in the rat ascribed to in situ formation of immune complexes. Very recently the demonstration that the aminonucleoside of puromycin provides some protection against PHN has highlighted the role of intrinsic properties of the glomerulus in immune complex formation. Adriamycin, a widely employed chemotherapeutic agent, is known to induce a nephrotic syndrome in rats characterized by severe ultrastructural changes of glomerular epithelial cells and by loss of glomerular polyanionic charges. We have studied the effect of pre-treatment with adriamycin on glomerular immune deposits in PHN using immunomorphological and quantitative techniques. In normal rats (group 1) injection of heterologous antibodies to proximal tubular brush border antigen (anti-FxIA), rapidly induces subepithelial immune deposits, as observed by immunofluorescence. Pre-treatment of rats with adriamycin (group 2) 48 hr before injection of anti-FxIA antibodies, when proteinuria is absent, does not alter the immunohistological findings of PHN. Heavily proteinuric rats (group 3) pre-treated with adriamycin 13 days before injection of anti-FxIA did not show any significant difference from groups 1 and 2. Species binding of injected anti-FxIA antibodies, studied by paired label techniques, was similar in normal rats and in proteinuric and non-proteinuric rats treated with adriamycin. The only difference was in the group of proteinuric rats treated with adriamycin, in which at 5 hr binding in the kidney was higher, due to tubular brush border binding as shown by immunofluorescence. This study indicates that local changes of the glomerulus and loss of glomerular histochemical properties do not invariably alter the glomerular deposition of immune complexes.

Animals↗
PubMed1982

[Protective effect of procyanidolic oligomers on the heterologous phase of glomerulonephritis induced by anti-glomerular basement membrane antibodies].

Treatment by procyanidolic oligomers can significantly decrease the proteinuria indiced in the Rat by intravenous injection of anti glomerular basement membranes antibodies. Immunohistological analysis shows that procyanidolic oligomers do not interfere with the mechanisms of immunopathological injury involved in this model (antibody binding to glomerular basement membrane, complement activation, glomerular influx of polymorphonuclear leucocytes). Their protective effect may be due to an increased resistance of the glomerular capillary to the inflammatory mediators released by neutrophils.

Animals↗
PubMed1982

Severity of glomerulonephritis induced in different strains of suckling mice by infection with lymphocytic choriomeningitis virus: correlation with amounts of endogenous interferon and circulating immune complexes.

Renal lesions due to neonatal infection with lymphocytic choriomeningitis virus were studied in three different strains of mice known to produce different amounts of viral interferon. Very severe ultrastructural lesions similar to those induced by exogenous interferon were found as early as day 8 in C3H mice which produced the highest amount of interferon. Further studies could not be performed in these mice since all died by day 14. Balb/c mice produced the lowest amount of interferon and had very mild ultrastructural lesions. An intermediate pattern was found in Swiss mice. After 30 days of infection, severe immune complex type glomerulonephritis detectable by light microscopy and immunofluorescence was observed in Swiss mice whereas mild lesions only were found in Balb/c mice. Circulating immune complexes were present in both strains but in greater amounts of Swiss than Balb/c mice. These results suggest that two factors at least are important in the development of glomerulonephritis: interferon produced early in life and the load of circulating immune complexes.

Animals↗
PubMed1982

Mercuric chloride induced autoimmune disease in Brown-Norway rats: sequential search for anti-basement membrane antibodies and circulating immune complexes.

Mercuric chloride induces in the Brown-Norway rat a biphasic autoimmune disease characterized initially by linear IgG deposits along the glomerular basement membrane followed later by granular IgG deposition. In the present study, anti-glomerular basement membrane antibodies and immune complex-like material were sequentially assessed in serial serum samples. Both were transiently found at the same period. Glomerular linear IgG deposits were present on day 11 but circulating anti-glomerular basement membrane antibodies were only found later on day 16. Circulating immune complexes were first detectable on day 8 before the earliest granular IgG deposits were first observed in the spleen vessels on day 16. The disappearance of circulating anti-glomerular basement membrane antibodies and of circulating immune complexes, although HgCl2 injections were pursued, is in agreement with the self-limited character of mercuric chloride induced autoimmune disease and suggests the induction of immunosuppressive mechanisms.

Animals↗
PubMed1982

Spontaneous circulating immune complex like material in Brown-Norway rats. Role of environmental factors.

Brown-Norway rats maintained under conventional housing conditions showed a significant increase in the C1q binding activity of serum and to a lesser extent of the Raji cell assay whereas no change was observed, in BN rats maintained under specific pathogen free (SPF) conditions. Glomerular IgG deposits were encountered among rats with circulating immune complexes (CIC). This suggests that microbiological environment is a major factor in the spontaneous appearance of CIC which could be of pathogenic significance.

Animals↗