concanavalin-a and Nephrosis--Lipoid

Lymphocyte ectoenzymes with immunomodulatory function were investigated in 11 children with minimal change disease (MCD), 9 with primary focal segmental glomerulosclerosis (FSGS), and 17 age- and sex-matched healthy children. Basal, concanavalin A (Con A)-, and pokeweed mitogen (PWM)-stimulated lymphocyte ecto-5'-nucleotidase (5'-Nu), dipeptidyl peptidase IV (DPP IV), and alkaline phosphodiesterase I (APD) activities were determined. In MCD relapse ecto-APD activity of unstimulated lymphocytes was higher than controls. Ecto-APD of Con A-stimulated lymphocytes was below controls (23.0, range 7.2-48.7 nmol/min per 10(6) lymphocytes) in all active MCD (18.7, range 7.6-32.6), during corticosteroid treatment (14.6, range 4.5-54), and in remission (13.1, range 6.1-19.6), but was significant only in remission. Con A-stimulated DPP IV was significantly lower from controls (53.8, range 19.3-85.7 nmol/min per 10(6) lymphocytes) in all active MCD (38.1, range 10.8-82.1), during treatment (37.5, range 20.2-58.7), and in remission (39.4, range 24.3-69.6). In FSGS, unstimulated lymphocyte ecto-APD activity was greater than controls. However, Con A-stimulated lymphocyte ecto-APD and DPP IV activities were not significantly different from controls. Con A stimulation of lymphocyte ecto-APD and DPP IV activity was significantly reduced in MCD relapse and in remission, but not in FSGS. Basal, Con A-, and PWM-stimulated ecto-5'-Nu in MCD and FSGS were not different from controls. These results suggest a role for abnormal T cell function in MCD but not in FSGS. The difference in mitogen-stimulated expression of these ectoenzymes suggests a different pathogenesis of childhood MCD and primary FSGS.

Topics: 5'-Nucleotidase; Adolescent; Cells, Cultured; Child; Child, Preschool; Concanavalin A; Dipeptidyl Peptidase 4; Enzyme Activation; Female; Glomerular Filtration Rate; Glomerulosclerosis, Focal Segmental; Humans; Lymphocytes; Male; Nephrosis, Lipoid; Phosphodiesterase I; Phosphoric Diester Hydrolases; Pokeweed Mitogens; Proteinuria

Concanavarin-A (conA)-stimulated peripheral blood mononuclear cells (PBMNC) from patients with idiopathic nephrotic syndrome (INS) produce putative factors that increase vascular permeability. These factors are expressed in the nephrotic phase but are reduced in the convalescent phase. To identify the genes that are expressed only in the nephrotic phase, we performed cDNA subtraction using conA-stimulated PBMNC from three patients with INS. We isolated several gene transcripts in all three subtracted cDNA libraries. Among these genes, IgE-dependent histamine-releasing factor (HRF) was overexpressed in the nephrotic phase not only at the mRNA level but also at the protein level in another 10 patients with INS. Moreover, we found increased secretion of HRF from conA-stimulated PBMNC in the nephrotic phase. The results suggest that HRF is involved in the pathogenesis of idiopathic nephrotic syndrome.

Topics: Biomarkers, Tumor; Cells, Cultured; Child; Concanavalin A; DNA, Circular; Female; Gene Expression Regulation; Humans; Immunoglobulin E; Leukocytes, Mononuclear; Male; Neoplasm Proteins; Nephrosis, Lipoid; Nuclear Proteins; Recombinant Proteins; RNA, Messenger; Transcription, Genetic; Tumor Protein, Translationally-Controlled 1; Vascular Endothelial Growth Factor A

A lymphokine, the vascular permeability factor (VPF), which increases vascular permeability, has been characterized in minimal-change nephrotic syndrome (MCNS). Transforming growth factor-beta (TGF-beta) is an immunosuppressive cytokine that inhibits proliferation, cytokine production, and cytotoxic activity of T cells and natural killer cells. We, therefore, investigated the effects of TGF-beta1 on the release of VPF by peripheral blood T cells from MCNS patients. The aim of our study was to determine the in vitro immunosuppressive capacity of TGF-beta1 in patients with MCNS.. To further test the effect of TGF-beta1 on concanavalin A (Con A)-induced VPF release, normal and MCNS T cells were stimulated with 5 microg/ml of Con A in the presence or absence of TGF-beta1, and the culture supernatants were tested for the presence of VPF by the method of Lagrue et al. The disease controls included 16 patients with IgA nephropathy.. Significantly increased spontaneous and Con A-stimulated secretion of VPF was detected in T-cell cultures of MCNS patients with the nephrotic syndrome as compared with those of normal controls. Addition of TGF-beta1 to these cultures inhibited the release of VPF in a dose-dependent manner. The effect of TGF-beta1 on the release of VPF was specific, since a reversion was obtained with a neutralizing monoclonal antibody to human TGF-beta1.. Together, our data demonstrate that TGF-beta1 antagonizes the ability of T cells to release VPF, and suggest a role of TGF-beta1 in the pathophysiology of VPF in vitro.

Topics: Adult; Capillary Permeability; Case-Control Studies; Concanavalin A; Dose-Response Relationship, Drug; Endothelial Growth Factors; Female; Glomerulonephritis, IGA; Glucocorticoids; Humans; In Vitro Techniques; Lymphokines; Male; Nephrosis, Lipoid; Prednisone; T-Lymphocytes; Transforming Growth Factor beta; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors

In a previous study, we reported that interleukin (IL)-12 could upregulate the production of vascular permeability factor (VPF) derived from activated human peripheral blood mononuclear cells. Since IL-18, a novel immunoregulatory cytokine with potent interferon-gamma inducing activities, has been shown to be a strong cofactor for T helper type 1 cell development, we tested the hypothesis that IL-18 in combination with IL-12 can act synergistically to modulate the production of VPF.. For this purpose, T cells were isolated from heparinized venous blood, stimulated with concanavalin A, and incubated in the presence of IL-18 or IL-12, and the production of VPF was determined by the method of Lagrue.. There was a significant increase in VPF production from concanavalin A-stimulated T cells following incubation with IL-18 or IL-12. More importantly, the combination of the cytokines was found to give a potent synergistic stimulation of VPF by concanavalin A-activated T cells from normal subjects. To determine the specificity of the stimulatory effect, neutralizing anti-IL-18 and anti-IL-12 antibodies were preincubated with IL- 18 and IL-12, respectively, prior to the addition of responder cells. The antibodies completely inhibited the effects of IL-18 and IL-12. Thus, these data show that IL-18 can synergize with IL-12 to selectively increase the production of VPF from T cells. The present study further demonstrates that IL-18 and IL-12 are in fact acting in synergy in patients with minimal-change nephrotic syndrome.. Taken together, our results indicate that both IL-18 and IL-12 contribute to the VPF production in vitro and suggest that they play key roles in the complexity of cytokine regulation in the pathophysiology of VPF.

Topics: Adult; Case-Control Studies; Concanavalin A; Dose-Response Relationship, Drug; Drug Synergism; Endothelial Growth Factors; Female; Humans; In Vitro Techniques; Interleukin-12; Interleukin-18; Kinetics; Lymphokines; Male; Nephrosis, Lipoid; T-Lymphocytes; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors

Increased production of a vascular permeability factor (VPF) from peripheral blood mononuclear cells (PBMC) in patients with minimal-change nephrotic syndrome (MCNS) has been reported. Interleukin-4 (IL-4) and interleukin-10 (IL-10), both produced by T-helper type-2 cells, are cytokines with the capacity to downregulate proinflammatory responses. To gain insight into the immunoregulatory properties of these cytokines, we analyzed the effects of recombinant human IL-4 and IL-10 on VPF release in MCNS patients. In the present study we show that the regulatory cytokines IL-4 and IL-10 are potent inhibitors of the VPF activity of concanavalin A-activated MCNS PBMC. Each cytokine was found to suppress VPF release in a dose-dependent manner. Moreover, when used at suboptimal concentrations, a combination of the two cytokines resulted in enhanced suppression of VPF release. Neutralization of endogenously produced IL-4 and IL-10 by both anti-IL-4 and anti-IL-10 antibodies resulted in an increased release of VPF. These data demonstrate that IL-4 acts in concert with IL-10 to inhibit VPF release and suggest that they are effective biologic regulators of the VPF responses in vitro.

Topics: Adolescent; Adult; Concanavalin A; Dose-Response Relationship, Drug; Down-Regulation; Endothelial Growth Factors; Female; Glomerulonephritis, IGA; Humans; Interleukin-10; Interleukin-4; Leukocytes, Mononuclear; Lymphokines; Male; Nephrosis, Lipoid; Statistics, Nonparametric; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors

The vascular permeability factor (VPF) is a lymphokine that has been shown to play a role in minimal-change nephrotic syndrome (MCNS). A better understanding of the mechanisms that upregulate VPF release is of basic importance to control the immune system in nephrotic syndrome (NS). Interleukin (IL)-15 is a key inducer of differentiation of uncommitted T helper cells, which regulates cellular immunity. The cytokine IL-15 appears to mimic the stimulatory activity of IL-2 on T cells.. In the present report, we studied the ability of IL-15, alone or in combination with IL-12, to influence the release of VPF by peripheral blood mononuclear cells (PBMC) from nephrotic patients. We have analyzed the release of VPF by concanavalin-A- (Con A) stimulated PBMC in normals, 16 patients with MCNS and 16 patients with IgA nephropathy (IgAN).. In both patient groups 50% had a proteinuria below 0.8 g/day. We demonstrate that nephrotic, but not non-nephrotic patients (both MCNS and IgAN), exhibit a high VPF release, which can be stimulated further by IL-15 + IL-12. To determine the specificity of the stimulatory effect, neutralizing anti-IL-15 and anti-IL-12 antibodies were preincubated with IL- 15 and IL-12 prior to the addition of responder cells, respectively. The antibodies completely inhibited the effects of IL-15 and IL-12.. These results indicate that IL-15 plus IL-12 acted additively to augment VPF release. These biological interactions between IL-15 and IL-12 may be important in the pathophysiology of VPF in vitro.

Topics: Adolescent; Adult; Cells, Cultured; Concanavalin A; Drug Synergism; Endothelial Growth Factors; Female; Glucocorticoids; Humans; Interleukin-12; Interleukin-15; Leukocytes, Mononuclear; Lymphokines; Male; Nephrosis, Lipoid; Nephrotic Syndrome; Prednisolone; Protein Isoforms; Reference Values; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors

The vascular permeability factor (VPF) is a lymphokine that has been shown to play a role in lipoid nephrosis (LN). Prior studies have shown that interleukin (IL) 12 promotes T helper type 1 differentiation and enhances production of T helper type 1 cytokines such as gamma interferon and IL-2. We, therefore, investigated the effects of recombinant human IL-12 on the release of VPF by peripheral blood mononuclear cells (PBMC) from LN patients. The VPF activity was measured according to the method of Ovary, with minor modifications. The goal of the present study was to examine the importance of IL-12 in concanavalin A induced VPF release in vitro. The levels of VPF were measured in a group of healthy subjects, LN patients with or without the nephrotic syndrome, and patients suffering from IgA nephropathy. There was a significantly increased concanavalin A induced release of VPF in LN and IgA nephropathy patients with nephrotic syndrome as compared with normal controls. Recombinant human IL-12 was found to enhance VPF release in a dose-dependent manner. Neutralization of endogenously produced IL-12 by anti-IL-12 antibody resulted in a decreased release of VPF by LN PBMC. These data indicate that endogenously produced IL-12 functions as a costimulatory molecule in vitro. Our data show that IL-12 can upregulate the release of VPF derived from LN PBMC. Thus IL-12 might be a potent adjuvant for inducing VPF. Therefore, IL-12 antagonists may interfere with newly initiated and ongoing VPF release associated with nephrotic syndrome.

Topics: Adolescent; Adult; Antibodies; Concanavalin A; Endothelial Growth Factors; Female; Glomerulonephritis, IGA; Humans; Interleukin-12; Leukocytes, Mononuclear; Lymphokines; Male; Nephrosis, Lipoid; Neutralization Tests; Recombinant Proteins; Steroids; Stimulation, Chemical; Up-Regulation; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors

Supernatants of peripheral blood mononuclear cell culture from children with minimal change nephrotic syndrome (MCNS) and focal segmental glomerulosclerosis (FSGS) were tested for their ability to increase glomerular basement membrane (GBM) permeability and for effects on anionic sites in the GBM. Supernatants from cultures of concanavalin A-stimulated peripheral blood mononuclear cells from patients with MCNS, those with FSGS and normal controls were infused into the renal arteries of normal rats. Infusion of the supernatants from patients with MCNS and FSGS caused a significant reduction of anionic sites in the GBM (p less than 0.001) and a significant increase in urinary albumin excretion (p less than 0.05), whereas infusion of supernatants in control cases did not reduce anionic sites nor increase urinary albumin excretion. These findings show that stimulation of peripheral blood mononuclear cells from MCNS and FSGS with concanavalin A results in liberation of soluble substances which reduce polyanions in the GBM and increases GBM permeability.

Topics: Albuminuria; Animals; Cell Membrane; Cell Membrane Permeability; Cells, Cultured; Child; Concanavalin A; Culture Media; Glomerulosclerosis, Focal Segmental; Humans; Kidney Glomerulus; Male; Monocytes; Nephrosis, Lipoid; Rats; Rats, Inbred Strains; Reproducibility of Results

A glomerular permeability factor produced by human T cell hybridomas. T cell hybridomas derived from the T cells of a patient with mammal change nephrotic syndrome (MCNS) made a glomerular permeability factor (GPF). Sufficient quantities of GPF were available for further analysis and characterization. We obtained four stable clones of human T cell hybridomas which produced a glomerular permeability factor. When this factor was injected intravenously into rats, significant proteinurias were induced, and in normal human lymphocyte culture, GPF enhanced Concanavalin-A (Con-A) induced lymphocyte blastogenesis by greater than ten fold. GPF was cytotoxic to tumor cell lines of epithelial origin, but only cytostatic to tumor cells of hematopoietic origin. Electron microscopy studies, with polyethyleneimine (PEI) staining, indicated that GPF induced the changes in the arrangement of PEI particles and partial fusion of glomerular epithelial cells in the rats given this factor intravenously. The molecular weight of GPF were estimated to be between 60,000 and 160,000 daltons. The molecular weight of the factor and its TNF like activity, we speculated that the factor was a lymphokine, like lymphotoxins.

Topics: Animals; Concanavalin A; Drug Synergism; Epithelium; Humans; Hybridomas; Lymphocyte Activation; Lymphokines; Molecular Weight; Nephrosis, Lipoid; Proteinuria; Rats; T-Lymphocytes; Tumor Cells, Cultured

Rat spleen lymphocytes (RSL) stimulated by mitogens in vitro were cultured on cryostat sections of rat kidney. After 36 hours glomerular polyanions (GPA) were stained with colloidal iron (CI). The results showed that the RSL stimulated with Con A were able to reduce GPA stainability as that treated with neuraminidase solution, and the effect was dose-dependent on Con A, whereas the supernatant of lymphocytes induced with Con A and the lymphocytes induced with PHA were not able to reduce GPA stainability. The result is in favor of the recent concept that the pathogenesis of MCN is associated with the loss of GPA which results from the dysfunction of the subpopulation of T lymphocytes.

Topics: Animals; Concanavalin A; Female; Kidney Glomerulus; Lymphocyte Activation; Male; Nephrosis, Lipoid; Rats; Rats, Inbred Strains; Sialoglycoproteins; T-Lymphocytes

Peripheral blood mononuclear cells (PBMC) from patients with minimal-change nephrotic syndrome (MCNS) were tested for their ability to produce a factor which increases the urinary protein excretion levels of rats. It was shown that enhanced proteinuria can be produced in 8-hour urine specimens from rats by the injection of concentrated supernatants of cultured concanavalin-A-stimulated PBMC of patients with MCNS, but not from other nephrotics or normal subjects. The increase in urinary protein excretion was associated with a significant alteration of glomerular epithelial cells similar to that seen in MCNS. These results suggest that in MCNS, PBMC release a factor, which we termed a glomerular permeability factor (GPF), causing changes in glomerular permeability with resulting proteinuria.

Topics: Adolescent; Adult; Animals; Concanavalin A; Female; Humans; Kidney Glomerulus; Lymphocyte Activation; Male; Middle Aged; Nephrosis, Lipoid; Permeability; Proteinuria; Rats; Rats, Inbred Strains; Urine

Topics: Animals; Concanavalin A; Culture Techniques; Female; Kidney Glomerulus; Lymphocyte Activation; Male; Mitogens; Nephrosis, Lipoid; Rats; Rats, Inbred Strains; Sialoglycoproteins

Peripheral mononuclear blood cells isolated from nephrotic subjects with minimal-change nephrotic syndrome (selective proteinuria greater than 3.5 g/24 h) or various other forms of glomerulonephritis (non-selective proteinuria greater than 3.5 g/24 h) were stimulated with concanavalin A and cultured for 20 h in the presence of kidney tissue under standard conditions. Identical cultures were developed with phosphate-buffered saline from normal control donors. Triplicate cultures of each subject (3 X 10(6) cells/ml) were incubated with or without 5, 10, or 20 micrograms/ml concanavalin A per milliliter serum-free tissue culture medium upon cryostat sections from normal rat kidney. The cells were subsequently removed, and the tissue sections were washed and stained for sialoprotein using the colloidal iron method and evaluated for stainability of glomerular polyanion using light microscopy. The results show that peripheral mononuclear blood cells from subjects with minimal-change nephrotic syndrome had affected glomerular polyanion in vitro during incubation with kidney tissue in a significantly (p less than or equal to 0.005) higher number of cases (15/17) as compared with the number of glomerulonephritis patients who scored positive in 4 out of 14 cases, whereas this was the case in 3 out of 18 cases of the normal donors. It is concluded that stimulated cellular immune reactivity of peripheral mononuclear blood cells from subjects with minimal-change nephrotic syndrome in vitro is associated with the potential impairment in vitro of an important part of the glomerular filtration barrier. Since this cellular activity occurred to a significant lesser extent in other nephrotic subjects, this response is not related to the nephrotic state per se.

Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Concanavalin A; Dose-Response Relationship, Drug; Humans; In Vitro Techniques; Kidney Glomerulus; Lymphocytes; Middle Aged; Nephrosis, Lipoid; Sialoglycoproteins; Staining and Labeling

We have previously shown a significant increase in 35sulfate uptake in rat glomerular basement membrane (GBM) when glomeruli were cocultured with peripheral blood mononuclear cells (PBMC) from patients with idiopathic minimal lesion nephrotic syndrome (IMLNS) in relapse, but an uptake not different than normal controls if glomeruli were incubated with PBMC of patients in remission. In the present study we examined 35sulfate uptake by GBM after PBMC from 12 IMLNS patients in remission were stimulated with Concanavalin A (Con A) (10 micrograms/ml of culture media). There was a significant increase in 35sulfate GBM uptake when glomeruli were cocultured with Con A-stimulated IMLNS PBMC (geometric mean), 331 cpm/mg dry glomerular weight) as compared to glomeruli cocultured with IMLNS PBMC (geometric mean, 200) (p = 0.048); glomeruli alone stimulated with Con A (geometric mean, 182) (p = 0.008) or glomeruli alone (geometric mean, 146) (p = 0.002). No significant differences were seen between the groups when glomeruli were cocultured with PBMC from 12 normal adults. These data show that Con A stimulated PBMC from IMLNS patients in remission alter the sulfate metabolism of rat GBM. The stimulation of PBMC with Con A reproduces the increase in 35sulfate uptake observed when glomeruli are cocultured with PBMC from IMLNS in relapse. Sulfated compounds in the GBM may play a role in glomerular permeability. Since stimulated nephrotic PBMC alter the metabolism of GBM sulfated compounds, these findings may have pathogenic significance.

Topics: Adolescent; Adult; Animals; Basement Membrane; Biological Transport, Active; Child; Child, Preschool; Concanavalin A; Female; Humans; In Vitro Techniques; Kidney Glomerulus; Leukocytes; Male; Nephrosis, Lipoid; Rats; Sulfates

Topics: Animals; Concanavalin A; Humans; Nephrosis, Lipoid; Rats; T-Lymphocytes, Regulatory

Peripheral T lymphocytes from patients with minimal change nephrotic syndrome (MCNS) and controls were treated for their ability to produce vascular permeability factors (VPF) without concanavalin A stimulation. In vitro cultures of T lymphocytes from active MCNS produced VPF in the supernatant, whereas T lymphocytes from inactive MCNS or normal subjects did not. Furthermore, the plasma from patients with active MCNS markedly inhibited VPF production when compared with plasma taken from inactive MCNS or fetal calf serum alone. However, the plasma from MCNS in neither the active nor the inactive stage had any direct blocking effect on VPF activity. These results seem to suggest that the plasma from patients with MCNS in the active stage inhibits VPF production, but does not neutralize T lymphocytes derived VPF activity.

Topics: Child; Concanavalin A; Humans; In Vitro Techniques; Lymphokines; Nephrosis, Lipoid; T-Lymphocytes; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors

Recent evidence suggests that transferrin has immunoregulatory functions. In the nephrotic syndrome, excessive urinary losses can produce hypotransferrinemia. Whether low serum transferrin concentration in children with the nephrotic syndrome is related to their decreased immunoglobulin concentrations and to the decreased in vitro response of lymphocytes to a mitogen was studied. Twenty patients, 2 to 15 years of age, were studied. Fifteen patients had the nephrotic syndrome and 5 had other renal disorders. Of 13 patients with nephrotic syndrome in relapse, serum transferrin and gamma-globulin concentrations were decreased in 10 and 11 patients, respectively. Transferrin levels correlated with the concentrations of total protein (r = 0.87, P less than 0.001), albumin (r = 0.91, P less than 0.001), and gamma-globulin (r = 0.78, P less than 0.001). Urinary electrophoretic analyses suggested that hypogammaglobulinemia was not explained simply by urinary losses. In order to determine whether decreased serum transferrin concentrations might limit immunoglobulin synthesis, the effect of hypotransferrinemic sera on lymphocyte proliferation in vitro was tested. At low concentrations of serum, tritiated thymidine uptake was directly proportional to the serum transferrin concentration (r = 0.86, P less than 0.001 at 0.02% serum concentration). Addition of transferrin completely restored the ability of patients' sera to support lymphocyte proliferation. These results suggest that hypotransferrinemia might influence in vivo lymphocyte function and immunity in the nephrotic syndrome.

Topics: Adolescent; Blood Proteins; Child; Child, Preschool; Concanavalin A; gamma-Globulins; Humans; Immunoglobulins; Iron; Lymphocyte Activation; Nephrosis, Lipoid; Nephrotic Syndrome; Transferrin

The response of lymphocytes to Concanavalin A (Con A) was measured in patients with the nephrotic syndrome due to minimal change nephropathy (11 patients), focal glomerulosclerosis (15 patients) and membranous nephropathy (21 patients); autologous serum was not used in these studies. There was a significant reduction in lymphocyte transformation in each group of patients compared to normal controls (p less than 0.01 for each group), but there was no significant difference between the individual groups of patients. Impaired lymphocyte transformation to Con A appears therefore to be a general feature of the nephrotic syndrome and is not exclusive to minimal change nephropathy. Measurements of suppressor cell function in 4 patients with minimal change nephropathy, 9 patients with focal glomerulosclerosis and 12 patients with membranous nephropathy were performed at the same time as the above studies. In each group suppressor cell function was decreased, indicating that the impaired lymphocyte response to Con A is not due to increased suppressor cell activity. These findings do not support the hypothesis that an abnormality of lymphocyte function peculiar to minimal change nephropathy is pathogenetic in that disease and not in other causes of the nephrotic syndrome; it seems more likely that the abnormalities described are secondary to the nephrotic state.

Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Concanavalin A; Female; Glomerulonephritis; Glomerulosclerosis, Focal Segmental; Humans; Lymphocyte Activation; Male; Middle Aged; Nephrosis, Lipoid; T-Lymphocytes, Regulatory

Topics: Adult; Aged; Concanavalin A; Glomerulonephritis; Humans; Immunity, Cellular; Kidney Diseases; Lymphocyte Culture Test, Mixed; Middle Aged; Nephrosis, Lipoid; T-Lymphocytes, Regulatory

A factor found in the serum of rats made nephrotic by a single administration of puromycin aminonucleoside (PA) has been shown to inhibit the blastogenic response of normal rat spleen cells when stimulated with either phytohaemagglutinin (PHA) or concanavalin A (Con A). Spleen cells removed from the nephrotic animals also exhibited a reduced capacity to incorporate thymidine when cultured with normal serum. This potent inhibitor was not cytocidal, and inhibition was not due to a lack of components essential for normal growth. Inhibition was not due to the excess of low density lipoproteins found in the nephrotic serum. Increasing mitogen concentrations in the presence of the nephrotic serum had little effect on inducing thymidine uptake by the normal spleen cells, while washing of the cells removed from the nephrotic animals appeared to partially overcome suppression of blastogenesis. The inhibitory factor was found to be less effective if the spleen cells had already been triggered by mitogen to undergo transformation in normal serum before the addition of the nephrotic serum.

Topics: Animals; Cells, Cultured; Concanavalin A; Lipoproteins, LDL; Lymphocyte Activation; Male; Nephrosis, Lipoid; Phytohemagglutinins; Rats; Rats, Inbred Strains; Spleen

Topics: Adolescent; Adult; Concanavalin A; Humans; Hypersensitivity, Delayed; Immunity, Cellular; Male; Nephrosis, Lipoid; T-Lymphocytes, Regulatory

Suppressor cell activity (SCA) was analysed in 28 patients with lipoid nephrosis (LN) and 11 patients with chronic proliferative glomerulonephritis (CGN). We have assessed the ability of peripheral blood lymphocytes (PBL) stimulated by concanavalin A (Con A) to inhibit the proliferative response of normal allogeneic lymphocytes by both Con A and phytohaemagglutinin (PHA). It was found that the LN patients in the earlier phase of relapse had significantly increased levels of suppression index (SI) were compared with the values obtained with normal controls. In contrast, the mean suppression values in the PBL from LN patients in remission and CGN patients with or without nephrotic syndrome, whether the mitogen used was Con A or PHA, were similar to those of the control subjects. Moreover, when individual patients were followed through their clinical illness, LN patients had high levels of SI, particularly in the beginning of acute exacerbations; the SI levels than decreased sharply in the latter phase of relapse and again increased to relatively normal levels with the onset of clinical remission. These in vitro findings suggest that there exists an alteration in Con A-induced SCA in a group of patients with LN.

Topics: Adolescent; Adult; Child; Concanavalin A; Female; Humans; Hypoproteinemia; Kidney; Lymphocyte Activation; Male; Middle Aged; Nephrosis, Lipoid; Prednisolone; Proteinuria; T-Lymphocytes, Regulatory

Sera from patients with the nephrotic syndrome due to minimal change nephropathy (11 patients), membranous nephropathy (14 patients) and focal glomerulosclerosis (15 patients) inhibited the response of normal lymphocytes to the mitogen Concanavalin A. Although there was a tendency for the sera of patients with minimal change nephropathy to be more inhibitory than sera from the other two forms of nephrotic syndrome, this effect of nephrotic sera on normal lymphocytes is not confined to minimal change nephropathy. Until the exact nature of the inhibitor(s) is established, it is therefore not possible to state that impaired lymphocyte transformation by serum plays a pathogenetic role specifically in minimal change nephropathy. The susceptibility of nephrotic patients to infection may be due in part to the sera of the patients causing reduced lymphocyte function in vivo which leads to a defective immune response.

Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Concanavalin A; Glomerulosclerosis, Focal Segmental; Humans; Lymphocyte Activation; Middle Aged; Nephrosis, Lipoid; Nephrotic Syndrome