concanavalin-a and Uremia

This study analyzed the structural differences of the carbohydrate chains of circulating free alpha-submit (alpha-SU) hypersecreted in various non-tumoral (primary hypothyroids, postmenopausal women, patients with chronic uremia, normal fetuses) and tumoral (gut carcinoids, TSH-, GH- and pure alpha-secreting pituitary adenomas) clinical conditions. Carbohydrate structures of free alpha-SU were investigated by means of lectin affinity chromatography using Concanavalin A (Con-A), which allows the separation of free alpha-SU in three different fractions (unbound = UB, weakly bound = WB and firmly bound = FB) depending on the nature and maturation of glycosylated chains. The concentrations of alpha-SU in serum and in Con-A fractions were measured by a sensitive and specific IRMA. Free alpha-SU hypersecreted from postmenopausal women, primary hypothyroids, and patients with chronic uremia showed similar binding patterns to Con-A, the percentage of UB fractions (UB: 44.5 +/- 1.9%, 39.5 +/- 3.8%, 48.2 +/- 5.6% respectively) being higher than both WB and FB fractions (WB: 33.2 +/- 1.4%, 30.7 +/- 4.6%, 28.5 +/- 2.1%; FB: 22.3 +/- 0.7%, 29.8 +/- 6.6%, 23.3 +/- 4.2% respectively). In normal fetuses the amount of UB fraction was very high (UB: 70.7 +/- 5.4%). Free alpha-SU from patients with TSH- and GH-secreting adenomas showed a binding pattern to Con-A significantly different from that observed in postmenopausal women taken as controls, the WB fractions being significantly higher (WB: 56.9 +/- 16.8% and 71 +/- 12.4% respectively, P < 0.001). A typical pattern of elution on Con-A, characterized by a prevalence of immature alpha-SU molecules eluted in the FB fraction, was found in patients with pure alpha-secreting adenomas. This chromatographic behavior was significantly different from that seen in the controls, as well as in other pituitary tumors and in gut carcinoids (FB: 41.8 +/- 5.0%, 22.3 +/- 0.7%, 16.8 +/- 6.6%, 10.6 +/- 2.0% respectively). Moreover, in these latter patients the pattern of free alpha-SU binding was exactly the opposite of that observed in pure alpha-secreting adenomas, with a prevalence of mature alpha-SU molecules (UB: 59.1 +/- 4.4 vs 18.3 +/- 7.2%). In conclusion, our data on Con-A affinity chromatography clearly demonstrate that carbohydrate branching of circulating free alpha-SU varies in patients with pituitary adenomas as compared with patients with gut carcinoids or other non-tumoral conditions. Moreover, the finding of a greater prop

Topics: Adenoma; Adult; Carcinoid Tumor; Chromatography, Affinity; Concanavalin A; Fetus; Glycoconjugates; Glycoprotein Hormones, alpha Subunit; Humans; Hypothyroidism; Intestinal Neoplasms; Pituitary Neoplasms; Postmenopause; Protein Binding; Uremia

A positive correlation between successful kidney transplantation, few rejection episodes, greater susceptibility to infection and morbidity in patients with high tissue levels of aluminium (Al) indicate that the metal may play a role in the immune response. The aim of this study was to determine if experimental aluminium intoxication could result in significant changes in lymphocyte activity in uraemic and nonuraemic rats.. Lewis rats were divided into four groups: normals (N), nephrectomized control (U), and Al-treated (N + Al) and nephrectomized Al-treated (U + Al), which received a cumulative dose of 30 mg Al over a 4-week period. Al quantification, histology, histochemical analysis and immunological assays were performed after Al intoxication.. High tissue levels of Al and positive histochemical staining in bones were seen in Al-treated rats. Bone histology revealed osteomalacia in U + Al rats. No statistical differences were observed in mixed lymphocyte cultures from controls and Al-treated rats, whereas U and Al-treated rats showed a decrease in lymphoproliferative response to mitogen and natural killer cell cytotoxic activity. A decreased helper T lymphocyte: cytotoxic T lymphocyte cell ratio and a reduction in interleukin-2 production were observed only in the U + Al group. A reduced number of total T lymphocytes was detected in the spleens of all Al-treated rats.. These findings suggest that aluminium toxicity may contribute to immunological impairment in chronic renal failure.

Topics: Aluminum; Animals; Bone and Bones; Cell Division; Cells, Cultured; Concanavalin A; Cytotoxicity, Immunologic; Immunity, Cellular; Interleukin-2; Kidney Failure, Chronic; Lymphocyte Activation; Lymphocyte Count; Male; Nephrectomy; Osteomalacia; Rats; Rats, Inbred Lew; T-Lymphocytes; T-Lymphocytes, Cytotoxic; T-Lymphocytes, Helper-Inducer; Uremia

Carbohydrate structures of intrapituitary and circulating TSH were studied by Concanavalin-A (Con A) and ricin lectin chromatography under different clinical conditions. Con A permits the separation of molecules differing in the extent of their carbohydrate branching, whereas ricin gives an estimation of the degree of their sialylation. Intrapituitary TSH was more retained on Con A and less sialylated than circulating hormone, suggesting that carbohydrate chains of intrapituitary molecules are less mature than those present in the circulation. A greater proportion of TSH firmly bound to Con A, compared to control values, was found in sera from fetuses and patients with uremia, TSH-secreting adenomas, and central hypothyroidism. In primary hypothyroid patients, TSH binding to Con A was similar to that found in controls, but a greater percentage of sialylated forms was seen. In central hypothyroidism patients, TSH released in response to TRH was less sialylated. Interestingly, no sialylated TSH was found in normal fetuses. In conclusion, the present data show that both TSH carbohydrate branching and sialylation may vary in different clinical conditions. As some of the above clinical conditions are known to be accompanied by variations in the bioactivity of circulating TSH, the finding of changes in TSH carbohydrate structures further supports the view that glycosylation modulates the expression of TSH biological activity.

Topics: Adenoma; Carbohydrates; Chromatography, Affinity; Concanavalin A; Female; Fetus; Humans; Hypothyroidism; Isoelectric Focusing; Male; Molecular Structure; Pituitary Gland; Pituitary Neoplasms; Pregnancy; Ricin; Thyrotropin; Uremia

Normal peripheral blood mononuclear cells (PBMC) were primed with sera from 22 predialytic uremic patients, normal sera, concanavalin A, or both. Their suppressive activity was subsequently tested on fresh phytohemagglutinin-stimulated allogeneic responders (i.e., genetically unrelated to either primed cell or sera donors). Uremic serum induced suppressor cell activity in the normal PBMC. No correlation was found between serum urea/creatinine levels and their effects on suppressor cell activity. The induced activity, expressed as percent suppression, was similar to that induced by concanavalin A. In PBMC primed with both concanavalin A and uremic serum, an additive suppressive effect was evident. The suppressor subset(s) induced by uremic serum proved to belong to adherent cell population. Addition of indomethacin or catalase to responder systems did not abolish the suppressive effects, thus suggesting a mechanism of action other than prostaglandin or hydrogen peroxide release.

Topics: Adult; Aged; Concanavalin A; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; T-Lymphocytes, Regulatory; Uremia

Cellular immunity of thymus lymphocytes in uraemic rats was studied. Severe and moderate uraemia was induced in rats, and sham-operated and normal rats were used as the controls. As a result, the response of thymus lymphocytes to concanavalin A (Con A) significantly decreased in severely uraemic rats, but did not change in moderately uraemic rats. However, when the thymus lymphocytes were pretreated with thymosin fraction 5, the response to Con A was ameliorated in severely uraemic rats. There was a significant correlation between the effect of thymosin fraction 5 on Con A response and Con A response of thymus lymphocytes. In addition, serum from severe uraemic rats suppressed the response of normal thymus lymphocytes to Con A. These results indicate that severe uraemia may cause an impairment in maturation of thymus lymphocytes, which can be improved by thymosin fraction 5 in vitro.

Topics: Animals; Cell Division; Cells, Cultured; Concanavalin A; Immune Tolerance; Immunity, Cellular; In Vitro Techniques; Male; Rats; Rats, Inbred F344; T-Lymphocytes; Thymosin; Thymus Gland; Uremia

Effect of hemodialysis (HD) on some indices of immune response was studied in nine chronic uremics. Total lymphocyte, OKT4+, and OKT8+ cell numbers significantly decreased during the first 20 min of HD, and they were decreased till the third hour of the procedure, whereas the OKT4+/OKT8+ cell number ratio did not change significantly. Before HD, Con-A--activated suppressor cells exerted a stimulatory action on autologous responder cells measured in two-step culture. During HD, Con-A-activated suppressor cell activity transiently appeared, with its peak at 60 min after the start of HD. It was accompanied by a transient rise in lymphocyte count with spontaneous interleukin-2 (IL-2) receptor expression, whereas the number of cells expressing IL-2 receptor following phytohemaglutinin (PHA) stimulation was progressively decreased during HD. A significant correlation was found between the increment of Con-A-activated suppressor cell activity and the increment of spontaneous IL-2 receptor expression on lymphocytes during one single blood flow through the dialyzer. The results supply further evidence that HD may impose additional disturbances on immune regulation in chronic uremics.

Topics: Adult; Chronic Disease; Concanavalin A; Female; Humans; Leukocyte Count; Lymphocyte Activation; Male; Receptors, Interleukin-2; Renal Dialysis; T-Lymphocytes; T-Lymphocytes, Regulatory; Uremia

Human peritoneal macrophages isolated from uremic patients undergoing peritoneal dialysis bind type 1 fimbriated Escherichia coli in the absence of opsonins. The number of bacteria bound per macrophage was 6.9, as determined by microscopic examination. Methyl alpha-mannoside (0.1 mM) and p-nitrophenyl alpha-mannoside (0.01 mM) inhibited this binding by about 66%. The ability of peritoneal macrophages to bind E. coli in a mannose-specific manner was confirmed in further experiments using an enzyme-linked immunosorbent assay (ELISA) with an antibacterial antibody, radiolabelled E. coli, and counts of colony-forming units (CFU). The number of bacteria bound per macrophage was 7 to 12 in the ELISA and 5.5-8.5 in the CFU assay. Methyl alpha-mannoside caused 70% inhibition of binding in the ELISA and 84% in the CFU assay, whereas p-nitrophenyl alpha-mannoside showed inhibition of 79% and 90%, respectively. Most bound bacteria (76-80%) were subsequently killed. Nonfimbriated E. coli 827 bound poorly to the macrophages (approximately 22%) as compared to that of the fimbriated bacteria. Although this binding was not inhibited by methyl alpha-D-mannoside or p-nitrophenyl alpha-mannoside, the percentage of bacteria killed was similar to that of the fimbriated phenotype. The peritoneal macrophage is thus able to phagocytose E. coli in the absence of opsonins. This may explain the relative rarity of E. coli as an etiologic agent of peritoneal infections in the dialysed patient.

Topics: Adult; Aged; Aged, 80 and over; Concanavalin A; Enzyme-Linked Immunosorbent Assay; Escherichia coli; Female; Fimbriae, Bacterial; Humans; Lectins; Macrophages; Male; Mannose; Middle Aged; Opsonin Proteins; Peritoneal Cavity; Peritoneal Dialysis; Phagocytosis; Stem Cells; Uremia

The effect of blood transfusion on humoral immunity in chronic renal failure was studied by examining immunoglobulin production in vitro, in patients awaiting renal transplantation. Pokeweed mitogen (PWM) induced IgG plaque formation was normal in non-transfused uraemic patients while both spontaneous and Staphylococcus aureus Cowan I (SAC) induced immunoglobulin production were reduced. Five to ten units of third party blood transfusion reduced PWM-driven B cell differentiation, but had no effect on SAC-induced plaque formation, while spontaneous production of immunoglobulin was either enhanced or unaffected. As it is known that the response to SAC is less affected by suppressor T cell activity than that to PWM, these differences in the inhibitory effects of blood transfusion on B cell differentiation are further evidence that transfusion may act by increasing suppressor T cell activity.

Topics: Adult; Antibody-Producing Cells; Antigens, Bacterial; Blood Transfusion; Concanavalin A; Female; Hemolytic Plaque Technique; Humans; Immunoglobulin G; Kidney Failure, Chronic; Male; Middle Aged; Pokeweed Mitogens; Staphylococcus aureus; Uremia

The immunologic alterations in patients on hemodialysis are only partially understood. We studied the Concanavalin A (Con A) induced suppressor cell activity of irradiated and nonirradiated cells in a mixed lymphocyte culture. Peripheral blood lymphocytes from 18 normal individuals and 14 patients on regular hemodialysis were incubated with two different concentrations of Con A (10 micrograms and 40 micrograms of Con A/million cells). Irradiated and nonirradiated cells were then tested for their capacity to suppress a standard MLC. The proliferative response to phytohemagglutinin, pokeweed mitogen and Con A was also determined. Suppressor cell activity of nonirradiated cells in hemodialysis patients was similar to that of controls, at both concentrations of Con A, while irradiated cells of hemodialysis patients showed a suppressor cell activity significantly lower than that of the controls, at a Con A concentration of 40 micrograms/10(6) cells (25.78 +/- 18.86% vs. 46.05 +/- 9.79%, p less than 0.001). The proliferative response of lymphocytes from hemodialysis patients to the three mitogens, did not show any difference when compared with normal controls. The normal proliferative response of lymphocytes from hemodialysis patients to mitogens and the normal suppressor cell activity of nonirradiated cells, suggest a normal T cell function. The abnormal suppressor cell activity in irradiated cells indicate that the radioresistant population has a functional defect. The cell responsible for this suppressor defect probably belongs to the monocyte/macrophage population because of its relative radioresistance.

Topics: Adult; Concanavalin A; Female; Humans; In Vitro Techniques; Lymphocyte Activation; Male; Middle Aged; Mitogens; Monocytes; Radiation Tolerance; Renal Dialysis; T-Lymphocytes, Regulatory; Uremia

Binding studies with six different purified 125I-labelled lectins, concanavalin A (con A), wheat germ agglutinin (WGA), Ricinus communis agglutinin II (RCA II), Dolichos biflorus (DB), Tetranolobus purpureus (TP) and P-phyto-hemagglutinin (P-PHA), were used to investigate the surface topography of carbohydrates in platelets from uraemic and normal subjects. Compared with normal the uraemic platelets, bear significantly decreased (more than 2.5-fold) numbers of receptors for P-PHA (N-acetyl D-galactosamine specificity) and Con A (specificity glucose, mannose). The number of WGA, RCA, II, DB and TP receptors in uraemic platelets did not differ from the number in normal platelets. Binding studies with 125I-labelled lectins provide further evidence of molecular defects in uraemic platelets. Moreover, this method might provide a fast and reliable technique for identifying abnormalities in the surface topography of carbohydrates on platelets in several pathological states.

Topics: Adult; Blood Platelets; Carbohydrates; Cell Membrane; Concanavalin A; Female; Humans; Lectins; Male; Phytohemagglutinins; Receptors, Mitogen; Uremia

An experimental model in rats was developed to define the nature of humoral and cellular factors that contribute to impaired immune responsiveness in chronic renal failure. Addition of uremic rat serum to both normal and uremic lymphocytes significantly suppressed cellular responses, the suppression being more pronounced with uremic lymphocytes. Lymphocytes from uremic rats were only marginally less responsive than normal lymphocytes to concanavalin A stimulation when normal rat serum was added to the cultures, indicating that the cellular factors in impairment were less important than humoral ones. Antibody formation in rat splenocyte cultures to bovine serum albumin was suppressed by addition of uremic serum, but the response to sheep erythrocytes was unaffected. Thus the effect on antibody response in uremic animals is dependent upon the antigen tested.

Topics: Animals; Antibody Formation; Cells, Cultured; Concanavalin A; Enzyme-Linked Immunosorbent Assay; Erythrocytes; Kidney Failure, Chronic; Lymphocyte Activation; Male; Rats; Rats, Inbred Lew; Serum Albumin, Bovine; Sheep; Spleen; Uremia

In the present experiment, we investigated the mechanism of the suppressed mitogen responses of peripheral blood mononuclear cells (PBMC) from uremic patients. We used phytohemagglutinin (PHA) and concanavalin A (Con A) as T cell mitogens, pokeweed mitogen (PWM) as a T cell-dependent B cell mitogen, and Staphylococcus aureus Cowan I (STA) as a T cell-independent B cell mitogen. PBMC from uremic patients showed significantly suppressed responses to PHA (p less than 0.05), Con A (p less than 0.05) and STA (p less tha 0.01) compared with those from healthy controls, but there was no significant difference in PWM response. However, these suppressed responses to PHA and Con A were markedly restored by depletion of phagocytic cells from PBMC. Although STA responses were also restored markedly in uremic patients, some patients still showed lower responsiveness to STA indicating the possibility of functional B cell defects. To further clarify the mechanism of the suppressed responses to mitogens, PBMC or nonphagocytic cells from uremic patients were cocultured with control T cells in the presence of PHA, or the effects of adherent cells from uremic patients on PHA responses of autologous or allogeneic control T cells were studied. From these experiments, it was suggested that the suppressed responses of PBMC to mitogens in uremia were mediated by monocytes.

Topics: Adult; Aged; B-Lymphocytes; Concanavalin A; Female; Humans; Lymphocyte Activation; Male; Middle Aged; Mitogens; Monocytes; Phytohemagglutinins; Pokeweed Mitogens; Staphylococcus aureus; Uremia

In vitro lymphoblastic transformation and sensitivity to methylprednisolone (MP) was studied in lymphocyte cultures obtained from patients on continuous ambulatory peritoneal dialysis (CAPD), on haemodialysis (HD) and control subjects. The PHA and Con A responses of peripheral blood lymphocytes (PBL) and T cells were identical in CAPD and control cultures, and in both significantly higher than in HD cultures (p less than 0.05). Both PBL and T cells from CAPD and control cultures were more resistant to the suppressive effects of MP than those from HD cultures. There was no relation between the duration of the dialysis period and the lymphocyte mitogen response in HD patients. Enhanced in vitro cell transformation and resistance to steroids during CAPD treatment may reflect an improved form of dialysis of importance for the general immune defence of the uraemic patient.

Topics: Adult; Concanavalin A; Female; Humans; In Vitro Techniques; Lymphocyte Activation; Male; Middle Aged; Peritoneal Dialysis; Peritoneal Dialysis, Continuous Ambulatory; Phytohemagglutinins; Uremia

Suppressor cells were assayed by numerical and functional tests in adults on chronic hemodialysis. Peripheral blood mononuclears (PBM) were classified as total T-cells by E-rosettes and by the monoclonal antibody OKT3, as T-cell subsets by OKT4 (inducer/helper T-cells) and OKT8 (cytotoxic/suppressor T-cells) and as B-cells by the presence of surface immunoglobulin. The suppressive effect of PBM pretreated with either Concanavalin A (Con A), sodium periodate, or serum rich in immune complexes, on normal homologous phytohemagglutinin (PHA) lymphocyte transformation, was determined. Usual tests of T-cell function were not done. T lymphopenia was due to significant diminution (P less than 0.002) in numbers of OKT4+ cells in patients (516 +/- 44 cells/mm3, mean +/- sem) as compared to controls (906 +/- 96 cells/mm3). The number of OKT8+ cells in patients was not different from normal although their percentage (45 +/- 4%) was slightly higher than controls (36 +/- 5%) (P less than 0.10). Suppressor activity using only a suboptimal dose of Con A (5 micrograms/ml), was significantly lower (P less than 0.002) in uremic patients (36 +/- 12%) than in controls (67 +/- 7%). An important finding was that no significant correlations were detected between the numerical and functional assays of suppression used or between any of these immunological tests and biochemical parameters studied. The implications of these results for immunoparesis in uremia are discussed with particular reference to the discordance between marker and functional assays of suppressor cells.

Topics: Adolescent; Adult; Antibodies, Monoclonal; Antigen-Antibody Complex; Concanavalin A; Female; Humans; Kidney Failure, Chronic; Lymphocyte Activation; Male; Middle Aged; Periodic Acid; Phytohemagglutinins; Rosette Formation; T-Lymphocytes, Regulatory; Uremia

Topics: Animals; Cell Adhesion; Chronic Disease; Concanavalin A; Creatinine; Immunity, Cellular; Lipopolysaccharides; Male; Mitogens; Phytohemagglutinins; Rats; Rats, Inbred WF; Spleen; Uremia

An experimental model of stable uraemia has been used to determine the effect of uraemia on cell-mediated immune mechanisms in the rat. Controlled resection of renal tissue allowed the establishment of a 'moderate' (blood urea 100-200 mg/100 ml) and 'severe' grade of uraemia (BU > 200 mg/100 ml). The immune responsiveness of isolated lymphocyte suspensions from uraemic animals was similar to that of sham-operated animals but lymphocyte function in both groups was suppressed compared with control non-manipulated animals. This was particularly evident in the graft vs host reaction. The host vs graft which assumes the cell-mediated immune status in the live animals, was also depressed in the uraemic animals but in contrast to the previous results sham-operated animals exhibited normal responses. The results underscore the importance of surgically induced anergy as a factor complicating the assessment of immune function in uraemia and may explain some of the inconsistencies observed in the evaluation of cell-mediated immunity by in vitro analysis of lymphocyte suspensions and tests of immune function in the intact host.

Topics: Animals; Concanavalin A; Graft vs Host Reaction; Host vs Graft Reaction; Immunity, Cellular; Lymphocyte Activation; Lymphocyte Culture Test, Mixed; Rats; T-Lymphocytes; Uremia

The activity of the leucocyte inhibitory factor (LIF) stimulated with Concanavalin A was examined in chronic uraemic, haemodialysed patients. It was found that the LIF activity decreased in chronic uraemic patients as compared with the normal controls. The absolute T lymphocyte count and active E rosette formation also decreased. In in vitro experiments the authors have also examined the inhibitory effect of the so-called "middle-sized molecule" (MSM) on uraemic materials separated from the serum and the haemofiltrate. They observed that the materials with a molecular weight of 1000-1500 isolated both from the serum and the haemofiltrate significantly inhibited the Con A stimulated LIF production of normal lymphocytes and decreased the ratio of the active E rosette-forming T lymphocytes. On the basis of their experiments the MSM uraemic materials are considered responsible for the decreased immune reactivity of uraemic patients. These uraemic toxins can be dialysed.

Topics: Adult; Concanavalin A; Female; Humans; Leukocyte Count; Leukocyte Migration-Inhibitory Factors; Lymphokines; Lymphopenia; Male; Middle Aged; Renal Dialysis; Rosette Formation; T-Lymphocytes; Toxins, Biological; Uremia

A model of experimentally induced uraemia has been used to study the effect of serum from uraemic rats on the immune responsiveness of thymus-derived (T) lymphocytes. Splenic lymphocytes from normal or uraemic animals responded to mitogenic stimulation with concanavalin A to a similar degree when cultured in a tissue culture medium containing the maximum non-toxic concentration of normal or uraemic serum in the culture system (3%). Serum from uraemic animals, however, had an immunosuppressive effect if the serum was first dialysed for 24 hr before being added to the tissue culture medium. When an alternative vessel was used which allowed the concentration of serum in the medium to be increased to 10%, serum from severely uraemic animals markedly suppressed the capacity of lymphocytes from normal animals to respond to Con A. Thus while serum from uraemic animals can be shown to be immunosuppressive, the results of the experiments are influenced by the conditions in vitro. The type of culture vessel and the concentration of serum in the culture medium are particularly critical determinants. It is likely that variations in laboratory procedures have contributed to the differences of opinion on the effect of serum from uraemic individuals on lymphocyte function.

Topics: Animals; Blood; Cells, Cultured; Concanavalin A; Female; Immune Tolerance; Lymphocyte Activation; Rats; Renal Dialysis; T-Lymphocytes; Uremia

The influence of uremic sera on the blastic response of lymphocyte of healthy subjects to nonspecific mitogens (PHA, Con A, PWM) in 3-day culture was investigated. Sera were obtained from 19 patients with renal insufficiency, among them 3 groups were distinguished: terminal renal insufficiency and acute renal insufficiency, both treated by hemodialysis, and severe chronic renal insufficiency treated conservatively. Generally, the statistically significant inhibitory influence of uremic sera on the blastic transformation values of lymphocytes of healthy subjects stimulated with nonspecific mitogens was found. There were no significant changes in inhibitory activity of sera obtained before and after hemodialysis. Inhibitory properties of uremic sera were similar in regard to blastic transformations stimulated with all mitogens used. The studies on the influence of the experimental stationary dialysis in vitro on the inhibition of blastic transformation by the uremic sera showed that under the specific conditions of diffusion, blastic transformation inhibitors passed through dialysis membrane and were removed from the sera. Among all tested sera there were only 2 which did not lower the blastic transformation values. The fact that they were obtained from the chronically dialyzed patients with the longest period of dialysotherapy supported the above observation.

Topics: Adolescent; Adult; Cells, Cultured; Concanavalin A; Female; Humans; Immune Sera; Immunosuppressive Agents; Lymphocyte Activation; Male; Phytohemagglutinins; Pokeweed Mitogens; Stimulation, Chemical; Time Factors; Uremia

The activity of LIF after Con A stimulation was examined in patients with hemodialysis and chronic uremia. It was found that LIF activity is reduced in uremia compared with healthy controls. The absolute number of T lymphocytes was reduced as well as the number of active E rosettes. An inhibitory effect was found in vitro by isolated middle molecules from uremic serum and ultrafiltrate. The LIF production of normal lymphocytes and the number of active rosettes are significantly reduced by substances isolated from serum and ultrafiltrate with molecular weight of 1 000 to 1 500 Dalton. The authors think that these uremic middle molecules are responsible for the already known reducing of immune response by uremia. The uremic substances are dialysable.

Topics: Adult; Chronic Disease; Concanavalin A; Female; Humans; Leukocyte Migration-Inhibitory Factors; Lymphokines; Male; Renal Dialysis; Toxins, Biological; Uremia

The effect of haemodialysis on mitogen-stimulated lymphocyte DNA synthesis was determined in twenty-four uraemic patients. Lymphocytes pre-haemodialysis were significantly less responsive to phytohaemagglutinin (PHA) than were control lymphocytes and showed the same degree of impairment as uraemic lymphocytes. Intrinsic lymphocyte responsiveness improved immediately after each haemodialysis. Pre-haemodialysis plasma inhibited control lymphocyte responsiveness and this inhibition was even greater in post-haemodialysis plasma. This effect of haemodialysis on plasma lasted for 4--8 hr. Similar alterations of response were noted, despite the use of different dialysers and also when two other mitogens were substituted for PHA. This deleterious effect of haemodialysis on lymphocyte function is important for its possible immune consequences, and may indicate a deficiency in current haemodialysis technique.

Topics: Adult; Aged; Concanavalin A; Female; Humans; Lymphocyte Activation; Lymphocytes; Male; Middle Aged; Phytohemagglutinins; Pokeweed Mitogens; Renal Dialysis; Time Factors; Uremia

Topics: Antibodies; B-Lymphocytes; beta 2-Microglobulin; Beta-Globulins; Binding Sites, Antibody; Concanavalin A; HLA Antigens; Humans; Immunoglobulin Fab Fragments; Immunosorbent Techniques; Kidney Transplantation; Lectins; Lymphocyte Activation; Transplantation, Homologous; Uremia