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M Zanetti

Publications and source records attributed to M Zanetti.

At least 217 records · Page 12Linked to original sources
PubMed1983

Anti-idiotypic immunity and autoimmunity. II. Idiotypic determinants of autoantibodies and lymphocytes in spontaneous and experimentally induced autoimmune thyroiditis.

In a previous report, it was demonstrated that heterologous anti-idiotypic antibodies to autoantibodies against rat thyroglobulin (ART) were capable of inhibiting the in vitro binding between ART and rat thyroglobulin. It has also been shown that repeated injections of anti-idiotypic antibodies into Buffalo (BUF) rats with spontaneous autoimmune thyroiditis were followed by a significant decrease in the levels of circulating ART. In this report, cross-reacting idiotypic determinants, detectable by rabbit anti-idiotypic antibodies to ART, are shown to also be present on ART from rats with experimentally induced autoimmune thyroiditis. In addition, antibodies to rat thyroglobulin from animals of various strains and species are shown to also express idiotypes cross-reacting with those of spontaneous ART of BUF rats. Finally, it is reported that idiotypic determinants similar to those of circulating ART are present on spleen lymphocytes from rats with autoimmune thyroiditis.

Animals↗
PubMed1983

Anti-idiotypic antibodies and autoantibodies.

In this paper, we have provided experimental evidence that antibodies to autoantigens bear common idiotypes and that this property makes them susceptible to anti-idiotypic regulation. Spontaneously occurring autoantibodies to Tg in rats have been extensively investigated as a model of immune response responsible for the appearance of autoimmune disease. Large idiotypic cross-reactivity was found among autoantibodies of various individual animals. Similarly, a high degree of idiotypic relatedness was found among mouse monoclonal antibodies reacting with a highly conserved antigenic domain of thyroglobulin. Both rat and mice idiotype were found to be present on spontaneous and induced antibodies to rat thyroglobulin from individuals of other species. In vivo experiments showed that anti-idiotypic antibodies can be effective in suppressing autoantibodies formation. In the induced TIN in BN rats, a single injection of anti-idiotypic serum prior to the induction of autoimmune disease was sufficient to generate a significant selective suppression of autoantibodies produced against a pathogenetic chemical form of the autoantigen, that is, the one against which the autoantibodies used to prepare the anti-idiotypic reagent as mostly reactive. Similarly, it was found that repeated injections of anti-idiotype into rats with ongoing spontaneous production of autoantibodies to thyroglobulin were able to significantly decrease the amount of circulating autoantibodies from the pretreatment values. Thus, although the beneficial effect of anti-idiotype observed in these experiments was only partial, indications were obtained that a specific anti-idiotypic immunity can be used to regulate autoantibody production. Finally, evidence has been provided to support the hypothesis that auto-anti-idiotype, as a normal constituent of the immune response, can be responsible for the potentiation of immune complex-mediated tissue injury that is often the hallmark of autoimmune diseases.

Animals↗
PubMed1983

High degree of idiotypic cross-reactivity among murine monoclonal antibodies to thyroglobulin.

The idiotypy of five mouse monoclonal antibodies (mAb) generated against human thyroglobulin (Tg) and reacting with Tg from various species, including murine Tg, was investigated. Rabbit antisera made specific for the idiotype (Id) of three mAb (62, 1.15, and 9.1) were used. By competitive inhibition of homologous Id-anti-Id binding, a surprisingly high degree of Id cross-reactivity was found. The Id determinants on mAb appeared located in or close to the paratope because anti-Id could inhibit their binding to Tg in each instance. Interestingly enough, no true "private" Id could be identified. Id cross-reactivity was found between mAb generated in different fusion experiments and recognizing apparently distinct epitopes on Tg. These results suggest that the immune response to phylogenetically highly conserved epitopes on antigen of internal origin, such as Tg, is idiotypically restricted.

Animals↗
PubMed1983

Participation of auto-anti-idiotypes in immune complex glomerulonephritis in rabbits.

We report the presence of auto-anti-Id antibodies in the glomerular immune deposits of a rabbit with chronic serum sickness induced by daily i.v. injections of bovine serum albumin. Auto-anti-Id antibodies were also documented in the serum of the same animal during the phase of chronic serum sickness in which immune complex glomerulonephritis develops. These results suggest that auto-anti-Id may normally participate in pathologic reactions and may be one of the mechanisms of potentiation and/or progression of immunopathologic lesions.

Animals↗
PubMed1983

Characterization of anti-tubular basement membrane antibodies in rats.

Autoimmune tubulointerstitial nephritis was induced in Brown-Norway (BN) rats by immunization with bovine (Bov) tubular basement membrane (TBM) in complete Freund's adjuvant. Serum antibodies thus produced reacted to a greater extent with Bov than BN TBM antigens by indirect immunofluorescence and by radioimmunoassay with particulate (P) and collagenase-solubilized (CS) TBM. The quantities of antibodies reactive with CS TBM correlated with the intensity of tubulointerstitial pathologic changes. Antibodies eluted from kidneys reactive with BN TBM by indirect immunofluorescence were 508 times more concentrated in the kidney than in the serum, compared with 15 times for Bov TBM-reactive antibodies. The reactivity of eluted antibodies to P BN TBM was inhibited by 70% after absorption with BN CS TBM. A major CS TBM antigen of 42,000 m.w. was identified by polyacrylamide gel electrophoresis. This antigen was present in both Bov and BN TBM, and may be important in triggering autoantibody formation in this model. Lewis rats immunized under the same conditions produced antibodies reactive with BN TBM by immunofluorescence but failed to develop immune deposits in TBM of their own kidneys. Analysis of serum anti-TBM antibodies in Lewis rats revealed a selective lack of reactivity with either homologous or autologous CS TBM. These results suggest that the ability to make an immune response to one or more elements of CS TBM plays a major role in the development of autoimmune tubulointerstitial nephritis in rats.

Animals↗
PubMed1983

Anti-idiotype as a probe in the analysis of autoimmune tubulointerstitial nephritis in the Brown Norway rat.

Rabbit antibodies specific for the idiotype (Id) of autoantibodies to tubular basement membrane (TBM) eluted from kidneys of Brown Norway rats with tubulointerstitial nephritis (TIN) were used to analyze the immune response to TBM antigens at the humoral and cellular levels. These antibodies appeared to recognize Id determinants associated with the antigen combining site on the anti-TBM Id as well as on splenic lymphocytes. However, efforts to detect Id-positive cells in the interstitial infiltrates of kidneys with TIN failed. In contrast, in vivo injection of anti-Id serum before immunization with TBM resulted in a) significant selective suppression of antibodies to the autologous collagenase-solubilized TBM moiety but not to antigenic determinants of the intact TBM nor to those of heterologous TBM, and b) a corresponding decrease of TIN. These results suggest that anti-Id antibodies of this type can be useful as a probe for further dissecting the pathogenetic mechanisms underlying these complex autoimmune responses.

Animals↗
PubMed1982

A recurrent idiotype on monoclonal anti-human Ia antibodies.

We report a recurrent idiotype on a remarkably high fraction (4/19) of murine monoclonal antibodies specific for human Ia monomorphic determinants and elicited by separate immunizations. For three of them, the shared idiotype is associated with the antigen-combining site. These results indicate that the spectrum of mouse antibody responses to human Ia antigens may be based on recurrent idiotypes, suggesting a limited potential repertoire of murine monoclonal antibodies to human Ia antigens. Anti-idiotypic reagents might be helpful in dissecting this repertoire and to generate a mirror image of a human Ia antigenic map. Furthermore, antisera to the idiotype of antibodies specific for human Ia monomorphic determinants might help in elucidating the interactions between Ia molecules and receptors on immune cells.

Animals↗
PubMed1982

Active extrusion of Ca2+ from epiphysial chondrocytes of normal and rachitic chickens.

Chondrocytes isolated from the epiphysial cartilage of chickens were exposed to either the ionophore A23187 or KCN, in the presence of 0.4 mM-extracellular Ca2+. This treatment elicits a prompt release of cell Ca2+, which can be measured as net cation efflux by a highly sensitive Ca2+-selective electrode system. Pre-exposure of chondrocytes to the metabolic inhibitors 2-deoxy-D-glucose or oligomycin causes a parallel decrease in both cell ATP and ionophore-mediated Ca2+ extrusion. Conversely, substitution of extracellular Na+ with choline produces only a very small decrease in the rate of Ca2+ efflux. This indicates that the ionophore A23187 and cyanide induce the mobilization of intracellular Ca2+, which is then extruded from the cell mainly by an ATP-driven pump system. Chondrocytes isolated from the cartilage of rachitic chickens also exhibit the capacity for extruding Ca2+ by the same mechanism, with an efficiency comparable with that of their normal counterpart.

Adenosine Triphosphate↗
PubMed1982

Suppression of nephrotoxic serum nephritis in rats by prostaglandin E1.

The ability of specific prostaglandins to modulate the development of nephrotoxic serum nephritis (NSN) in rats has been examined. The nephrotoxicity of one intravenous injection of antibodies directed against rat glomerular basement membrane (GBM) was markedly suppressed by treatment with a stable analog of prostaglandin E1 (15-(S)-15-methyl PGE1; 15-M-PGE1). Prostaglandin E1 treatment was shown to suppress both glomerular hypercellularity and proteinuria, while the binding of specific antibody to the GBM was not altered. These studies indicate that certain prostaglandins may play an important role in the regulation of Type II immune reactions. Further investigations of the role of arachidonic acid products undoubtedly will provide valuable information regarding the modulation of tissue injury as a result of various inflammatory reactions.

Alprostadil↗
PubMed1981

Anti-idiotypic immunity and autoimmunity. I. In vitro and in vivo effects of anti-idiotypic antibodies to spontaneously occurring autoantibodies to rat thyroglobulin.

The effects of anti-receptor (anti-idiotypic) immunity on autoimmune responses have been investigated in Buffalo (BUF) rats with autoimmune thyroiditis. As compared to other animal models of autoimmune disease, BUF rat thyroiditis has the following advantages: it occurs in an inbred strain, arises spontaneously (i.e. without the experimental administration of autoantigens and adjuvants) and is characterized by production of autoantibodies to only one autoantigen, thyroglobulin. Finally, its pathogenesis is mediated by autoantibodies to rat thyroglobulin, and therefore this model is particularly suitable to study the effects of anti-idiotypic reactions on those autoimmune disorders whose damage is caused by humoral immunity. The experiments reported in the present study show that first, heterologous anti-idiotypic antibodies to autoantibodies against rat thyroglobulin have been produced and characterized. It has then been demonstrated that such anti-idiotypic antibodies are capable of inhibiting the in vitro binding between thyroglobulin and thyroglobulin autoantibodies obtained from BUF rats. It has also been shown that repeated injections of anti-idiotypic antibodies into sublethally X-irradiated BUF rats with autoimmune thyroiditis were followed by a significant change in the levels of circulating autoantibodies to rat thyroglobulin. These results provide evidence that in spite of the complexity of autoantigens and the heterogeneity of autoimmune responses, established autoimmune diseases may be controlled by sequential immunosuppression and anti-idiotypic immunity.

Animals↗
PubMed1981

Ca2+-binding studies of the phosphoprotein from rat-incisor dentine.

Rat incisor dentine was demineralized and extracted with 0.25 M EDTA containing protease inhibitors. The extract was purified by chromatography on DEAE-cellulose and sulfonated polystyrene. The Ca2+-finding properties of the phosphoprotein were studied by dynamic dialysis and by using a Ca2+-selective electrode. Two different binding sites were detected with Kd = 0.9 X 10(-7) M and 1.1 X 10(-5) M and displaying a Ca2+-binding capacity of 127 and 176 mol bound Ca2+/mol protein, respectively, assuming a molecular weight of 30 000. Upon enzymatic dephosphorylation of the phosphoprotein, the highest affinity sites disappeared and those with the lowest affinity were reduced. The optimum for Ca2+ binding by the phosphoprotein occurred at pH 8.2. The specificity of the Ca2+ ion interaction with the phosphoprotein was investigated by studying the competitive nature of other divalent and monovalent cations. It was found that Ca2+ ions were to a large extent displaced from the phosphoprotein by other cations in physiological concentrations.

Animals↗
PubMed1981

Demonstration of a passive Heymann nephritis-like mechanism in a human kidney transplant.

The underlying mechanism of human extramembranous glomerulonephritis (EMGN) is generally thought to involve circulating immune complexes. Data presented here suggest that "in situ" formation of immune deposits may also be important in the pathogenesis of EMGN. We describe a patient with a "de novo" EMGN in a kidney transplant a few months after the graft placement. Before transplantation, the patient's serum contained antibodies reacting in vitro with rat kidney brush-border, but serum concentration of these antibodies rapidly decreased prior to the onset of proteinuria. No circulating immune complexes were detected on serial serum samples from the patients. Antibodies which were eluted from the kidney transplant biopsy were shown to react with the brush-border of the proximal convoluted tubule of rat kidney. We postulate that "in situ" formation of immune complexes within the glomerular capillary walls, and not circulating immune complexes, is the pathogenic mechanism responsible for the glomerular lesions of this case of EMGN.

Adult↗
PubMed1980

Influence of calcium depletion on medullary bone of laying hens.

Medullary bone of birds maintained on a low-calcium diet represents a good model to study modifications of matrix composition in calcified tissue undergoing intense formation and resorption. The composition of the bone matrix during the low-calcium diet has been analyzed by both chemical and histological techniques. Sixty White Leghorn pullets 1 year old were used for the experiment. Fifteen birds served as controls and were killed on day zero; the remaining birds were placed on a calcium-deficient diet (0.13% calcium) and sacrificed after 4, 7, and 12 days of treatment in groups of 15. Serum levels of calcium, PTH, and estrogens were also measured. Chemical analysis of the samples were made for total nitrogen, hydroxyproline, hexosamine, hexoses, calcium, and phosphorus. Collagen and proteoglycans of the matrix of medullary bone of the egg-laying hens were found to be affected by the low-calcium diet. They either increased or decreased during the experiment but never in parallel. The increment of serum PTH is considered responsible for the variations in the amount of collagen. The effects of this hormone are magnified by the fall of serum estrogens as shown also by variations in the amounts of noncollagenous protein. In the late phase of the diet the matrix is represented by poorly calcified osteoid tissue rich in noncollagenous protein, i.e., proteoglycans and glycoproteins.

Animals↗
PubMed1980

Distribution of blood group antigen A in normal and pathologic human kidneys.

We tested this distribution with an indirect immunofluorescent technique using purified rabbit anti-A antiserum on 21 whole normal kidneys (a group, N equal to 18; AB group, N equal to 1; O group, N equal to 2) and on 349 kidney biopsy samples (A group, N equal to 140; AB group, N equal to 14; O or B group, N equal to 195) representing a large spectrum of renal diseases. In normal kidneys from A and AB groups, the A antigen was detected in the whole vascular endothelium and in the convoluted distal tubules. In secretors, collecting tubules were brightly positive. Epithelial staining was more diffuse in the inner part than it was in the outer part of the medulla. The basement membrane of the inner collecting tubules was positive in frozen sections but not in paraffin sections. In pathologic kidneys, modifications were obvious: (1) The thickened basement membrane of atrophic convoluted distal tubules was brightly stained. (2) Endothelial staining allowed a precise appreciation of the glomerular and interstitial vasculature. (3) In proliferative changes such as arterial intimal proliferation, proliferative glomerulonephritis, and interstitial cell infiltration, endothelial cells do not proliferate. This routine staining technique of endothelial cells by anti-A antiserum provide information not obtainable with light microscopy.

ABO Blood-Group System↗
PubMed1980

Ca2+-binding glycoprotein in avian bone induced by estrogen.

The discovery in calcifying cartilage of a glycoprotein, endowed with high calcium affinity and alkaline phosphatase activity, has prompted the investigation of the presence of this compound in other calcified tissues. From medullary bone, a tissue which is highly mineralized under estrogen stimulus, a glycoprotein has been extracted which had the properties described. Besides the high calcium affinity (KD = 10(-7)M), this protein shows phosphatase activity and rate of hydrolysis of ATP, GTP and pyrophosphate was measured. Analysis of the chemical composition of the matrix of the medullary bone indicates that proteoglycans are present in large amounts. The calcium binding glycoprotein appears to be a compound present in different calcified tissues.

4-Nitrophenylphosphatase↗
PubMed1980

A search for circulating immune complex-like material during the course of autoimmune complex glomerulonephritis in Lewis and Brown Norway rats.

Circulating immune complexes were repeatedly searched for using the C1q-binding assay and the Raji cell test in Lewis and BN rats immunized with the Fx1A fraction from convoluted proximal tubule or with kidney homogenate, mixed with various adjuvants. An autoimmune glomerulonephritis was easily induced in Lewis rats. A potent adjuvant and a booster injection were necessary to obtain such a glomerulonephritis in the BN strain which is reputedly resistant. No circulating immune complex-like material could be found in Lewis rats using the C1q-binding assay. A high C1q-binding activity was found in Bn rats including control rats. The Raji cell test was weakly positive in Lewis and BN rats including control rats. This study demonstrates that the classical resistance of BN rats can be overcome if a potent adjuvant is used. Our failure to demonstrate circulating immune complexes suggests that in situ formation of immune deposits, as recently demonstrated in passive Heymann's nephritis, may also be operative in autoimmune complex glomerulonephritis. Other factors than the antigen used can be responsible for positive C1q-binding or Raji cell tests.

Animals↗