Presence Of Concanavalin Research Articles

Changes in the microheterogeneity of serum α1-acid glycoprotein in pregnancyglycoprotein in pregnancy

Immunodiffusion studies show that serum concentration of α1-acid glycoprotein remains virtually the same during all trimesters of pregnancy. A positive correlation (r=0.87) between the term of pregnancy and the concentration of the α1-acid glycoprotein fraction with bi-, tri- and tetra-antenna side chains is established using crossed affine immunoelectrophoresis in the presence of concanavalin A.

Immunostimulating polysaccharides from Panax notoginseng.

The main purpose of this study is to prepare and characterize polysaccharides from Panax notoginseng, investigate their effects on immune system in vitro in order to find new immunostimulants for the prevention and supporting treatment of infection and immunodeficiency related diseases. Polysaccharides were extracted with aqueous solution, separated with column chromatography. Their anticomplementary activities were investigated by using human serum and antibody-sensitized sheep red blood cells. Interferon-gamma and tumor necrosis factor inductive activities were studied by using isolated mouse spleen lymphocytes and peritoneal macrophages, respectively. Four polysaccharides, homogeneous in gel-filtration chromatography, were prepared and designated PF3111, PF3112, PBGA11, and PBGA12. Component sugar analysis revealed that they are heteroglycans with MWs ranging from 37 kD to 760 kD, composed of glucose, galactose, arabinose, mannose, and xylose in different molar ratios. Fraction PBGA12 has the most anticomplementary activity which is mediated through both alternative and classical pathways. All the polysaccharides except PBGA11 induced the production of interferon-gamma in the presence of concanavalin A. They induced the production of significant amount of TNF-alpha in cell cultures. The polysaccharides from P.notoginseng have immunostimulating activities in vitro.

Regulation of leukocyte interleukin 2 and interleukin 2 receptor gene expression by rabbit blastocoelic fluid

The mechanisms underlying the inhibition of lymphocyte proliferative response by rabbit blastocoelic fluid collected on day 12 of embryonic development were investigated. Treatment with blastocoelic fluid, even in the presence of concanavalin A, maintains lymphocytes in a quiescent state by preventing cell entry into the S phase of the cell cycle. Gene expression of interleukin 2 receptor is completely blocked by treatment with blastocoelic fluid as are the secretion and gene expression of interleukin 2. Addition of interleukin 2 to prestimulated interleukin 2 receptor positive lymphocytes failed to downregulate the expression of high-affinity interleukin 2 receptor and completely abolished the embryonic fluid-mediated inhibitory effect on [3H]thymidine incorporation. Taken together, these results suggest that embryonic fluid has differential inhibitory effects, depending on the activation state of the lymphocytes. Nevertheless, inhibition of interleukin 2 and interleukin 2 receptor expression by embryonic fluid restrains immune cell activity and therefore can be implicated in the survival of the fetal semi-allograft.

Effects of n-3 polyunsaturated fatty acids and lectins on immunoglobulin production by spleen lymphocytes of Sprague-Dawley rats.

We examined the effects of n-3 polyunsaturated fatty acid (PUFA), such as alpha-linolenic (alpha-LA), eicosapentaenoic (EPA), and docosahexaenoic acid (DHA) on immunoglobulin (Ig) production by spleen lymphocytes of Sprague-Dawley rats. n-3 polyunsaturated fatty acid (PUFA) strongly inhibited the production of IgA and IgM and that of IgG weakly at 100 microM. When the lymphocytes were treated with n-3 PUFA in the presence of other inhibitory biomaterials such as lectins, some PUFA attenuated their inhibitory effect on Ig production. In the presence of concanavalin A (ConA), all n-3 PUFA attenuated the inhibitory effect of ConA on the production of IgM or IgG but increased its inhibition of IgA synthesis. Thus, the interaction of n-3 polyunsaturated fatty acid and lectins in spleen interfere with each other or the expression of Ig production regulating activity.

Myosin II is involved in capping and uroid formation in the human pathogen Entamoeba histolytica

The redistribution and capping of surface receptors on the human pathogen Entamoeba histolytica was observed in the presence of concanavalin A (ConA). Capping was correlated with plasma membrane folding towards the rear of the amoeba and with uroid formation. The uroid is thought to play a role in the escape of amoebae from the host immune response. To localize myosin II during capping, amoebae were incubated in the presence of ConA and then analyzed by microscopy. Myosin II was three times more concentrated within the uroid compared with the rest of the cell, suggesting that the release of caps may depend upon mechanical contraction driven by myosin II activity. The use of drugs that disrupt cytoskeletal structure or that inhibit myosin heavy chain phosphorylation demonstrated that inhibition of capping prevents uroid formation. Biochemical analysis allowed the identification of two ConA receptors which have been previously described as major pathogenic antigens of this parasite: the 96-kDa antigen, which carries alcohol dehydrogenase 2 activity and binds extracellular matrix proteins, and the Gal-GalNAc-inhibitable surface lectin, which is involved in amoeba-cell interactions and in the degradation of complement particles attached to the parasite.

Effect of sonicated material from Fusobacterium nucleatum on the functional capacity of accessory cells derived from dental pulp.

Fusobacterium nucleatum-derived components were studied for their effect on the ability of accessory pulpal cells to induce T-lymphocyte proliferation. In initial experiments, spleen cells were used to establish concentration ranges at which testing of the effect of the bacterial components would be suitable. At low concentrations, bacterial substances induced a stimulatory effect on the proliferation rate of spleen cells, but not when purified T-lymphocytes were incubated in the presence of concanavalin A and pulpal accessory cells. At increasing concentrations, a dose-dependent reduction was observed. Pretreatment with the bacterial products for 4 h gave a stimulatory effect in the absence of concanavalin A for both spleen cells and T-lymphocytes. Removal of low-molecular weight components (<3.5 kDa) did not influence the inhibitory effect, whereas preheating the bacterial substances to 100 degrees C eliminated the observed inhibition. Findings show that heat-sensitive, high-molecular-weight components of F. nucleatum can evoke a concentration-dependent stimulatory or suppressive effect on the proliferation rate of T-lymphocytes in the presence of accessory cells derived from the dental pulp.

Laminin SIKVAV Peptide Induction of Monocyte/Macrophage Prostaglandin E2 and Matrix Metalloproteinases

The laminin-derived synthetic peptide containing the SIKVAV (Ser-Ile-Lys-Val-Ala-Val) amino acid sequence has been previously shown to regulate tumor invasion, metastasis, and angiogenesis. Here, we demonstrate that this peptide also modulates human monocyte responses. Moreover, the monocytic responses elicited by this peptide are influenced by the culture conditions. When elutriated monocytes were cultured on SIKVAV substrate or in suspension with this peptide, the synthesis of prostaglandin E2, interstitial collagenase, and gelatinase B was induced and was further enhanced in the presence of concanavalin A (ConA). However, when monocytes were adhered before adding soluble SIKVAV, the peptide alone failed to induce the production of prostaglandin E2 or matrix metalloproteinases. If adherent monocytes were exposed to SIKVAV in the presence of ConA, this peptide enhanced the ConA induced production of these mediators. In contrast to SIKVAV, the intact laminin molecule failed to influence these monocyte responses. This is the first demonstration that a laminin derived peptide is capable of inducing or enhancing monocyte inflammatory responses that may influence a number of biological activities such as wound healing or excessive connective tissue destruction associated with chronic inflammation.

Involvement of interleukin-1 in immobilization stress-induced increase in plasma adrenocorticotropic hormone and in release of hypothalamic monoamines in the rat

We investigated whether interleukin-1 (IL-1) activity in the rat hypothalamus was increased by immobilization stress (IS), and whether pretreatment with an interleukin-1 receptor antagonist (IL-1Ra) is capable of inhibiting IS-induced elevations of hypothalamic norepinephrine (NE), dopamine (DA), and serotonin (5-HT) and the levels of their metabolites as well as of plasma adrenocorticotropic hormone (ACTH). IL-1 activity was estimated with a bioassay using mouse thymocyte proliferation in the presence of concanavalin A. IL-1Ra was administered directly into the anterior hypothalamus, and monoamines were determined using a microdialysis technique and an HPLC system. First, we found that levels of IL-1 activity in the rat hypothalamus reached a maximum at 60 min after starting IS. Second, IL-1Ra (2 micrograms) significantly inhibited IS-induced increases in hypothalamic NE, DA, and 5-HT levels as well as the levels of their metabolites. In addition, IL-1Ra (2 micrograms) also inhibited the IS-induced elevation of plasma ACTH levels. Third, timing effects of IL-1Ra administration on the IS-induced monoamines or ACTH responses were examined. IL-1Ra (2 micrograms) administered at 5 or 60 min before the start of IS, but not at 5 or 60 min after IS had been started, exerted inhibitory effects on these responses, indicating that the effects of IL-1 occurred within 5 min after the initiation of IS. In summary, these results suggest that IS enhances biologically active IL-1 in the hypothalamus, and that hypothalamic IL-1 plays a role in the regulation of IS-induced responses including elevated monoamine release in the hypothalamus and activation of the hypothalamo-pituitary-adrenal axis. Moreover, since 5 min is too short a time for IS to induce production of IL-1, IS may augment the effects of preexisting IL-1 in the hypothalamus.

The Role of Cyclic Adenosine Monophosphate in the Suppression of Cellular Immunity After Thermal Injury

Cyclic adenosine monophosphate (cAMP) is an intracellular second messenger that is known to convey inhibitory signals for T-cell proliferation and function. We investigated the association between this molecule and the profound immunosuppression that accompanies thermal injury. Mice were randomized into two groups: one group was subjected to a 20% full-thickness scald burn; the second to a sham burn (control). The mice were killed on days 4, 7, or 10 after the burn injury and splenocytes were pooled and cultured for 15 minutes in the presence or absence of prostaglandin E2 (PGE2). Levels of cAMP in splenocytes were significantly elevated on day 7 after burn in the burn group compared with the sham controls (P < .05, Wilcoxon Rank Sum Test). Incubation of splenocytes with PGE2 resulted in significantly greater levels of intracellular cAMP in cells from the burn group compared with controls on days 4, 7, and 10. Incubation of normal splenocytes with dibutyryl cAMP in the presence of concanavalin A significantly decreased cell proliferation and the production of interleukin-2. The decrease in interleukin-2 production was evident at the level of messenger RNA expression. Stimulation of splenocytes with a combination of phorbol ester and calcium ionophore, bypassing all membrane-associated events prior to protein kinase C activation, reversed the inhibitory effects of dibutyryl cAMP. Incubation of splenocytes from burned animals with H-8, a selective inhibitor of cAMP-dependent protein kinases, restored the proliferative response to that of sham controls on days 4, 7, and 10 after thermal injury. These data indicate that elevated levels of intracellular cAMP, combined with an increased production of cAMP in response to circulating PGE2, may play a fundamental role in suppression of the immune response following thermal injury and that cAMP exerts its immunomodulatory effects prior to protein kinase C activation.

Diabetes enhancement and increased islet antigen expression following neonatal injections of glucose and arginine in non-obese diabetic mice

Modulation of β-cell antigens at birth may affect the course of type I diabetes. Since the functional state of β cells modulates antigen expression, we investigated whether neonatal injections of glucose and arginine (G-A) influence diabetes in non-obese diabetic (NOD) mice. Two groups of 90 mice (45 female, 45 male) were injected for the first 6 days of life with G-A or saline. To determine whether these injections influenced β cell functional maturation, isolated islets were characterized according to insulin response to glucose or arginine. Modulation of antigens for islet-cell autoantibodies (ICA antigens) was analyzed by indirect immunofluorescence using ICA-positive human sera. Variations of pancreatic glutamic acid decarboxylase 67-kD (GAD 67) mRNA were evaluated by polymerase chain reaction (PCR), hybridization with a 32P-labeled probe, and densitometry of the autoradiographic bands. Female NOD mice treated with G-A displayed diabetes earlier and with a higher incidence ( P < .01) than control mice, whereas the diabetes incidence was not statistically modified in G-A-treated male NOD mice. Insulitis was more severe ( P < .03) in 2-month-old G-A-treated female NOD mice than in control mice, but was not statistically modified in male NOD mice. In both sexes, ICA antigens and GAD 67 mRNA were higher in G-A-treated mice than in control mice ( P < .01). Islets isolated after neonatal G-A injections exhibited improved insulin sensitivity to both stimuli ( P < .01). Splenocyte subsets analyzed by cytofluorometry, as well as splenocyte proliferations in the presence of concanavalin or rat insulinoma cells or during syngeneic mixed-lymphocyte reaction, were not modified after G-A treatment. We conclude that neonatal injections of G-A enhance diabetes in female NOD mice. Even though hypotheses as to the direct effects on the immune system or deleterious effects of glucose and arginine on the β cells cannot be excluded, the mechanisms behind the clinical effect could be related to accelerated maturation of β cells and overexpression of islet antigens during the completion of immune self-tolerance, or to amplification of the destructive process due to the existence of more targets for effector cells. The same treatment does not significantly affect diabetes in male NOD mice whose resistance to disease could not be overcome simply by peripheral modulation of β-cell antigens.

Age-dependent immune response in Merino sheep

The numerical and functional attributes of populations of lymphocytes were compared in the blood, lymph and skin of young and mature sheep. Young sheep, four to eight months old, had a lower proportion of CD4 + cells in blood, lymph and skin than mature sheep three to six years old. In contrast, B cells and T19 + cells were as prevalent or more prevalent in young sheep as in mature sheep. Blood lymphocytes from young sheep, cultured in vitro produced less interferon-γ, both spontaneously and in the presence of concanavalin A than did lymphocytes from older sheep. The serum antibody responses of adult sheep to the T cell-independent antigen Brucella abortus lipopolysaccharide (LPs) were greater over a range of antigen doses, suggesting that an apparent excess of antigen could not overcome the relative immune deficiency of young sheep. The adjuvant Quil A corrected the depressed antibody response of young sheep to B abortus LPs, but dextran sulphate did not. The skin contact hypersensitivity of mature sheep to dinitrochlorobenzene was greater. However, the T cell phenotypes present in infiltrates of lymphocytes elicited by the intradermal injection of tetanus and diphtheria, but not tuberculin antigens, were comparable for the two age groups. The capacity of Quil A to raise the antibody responses of both young and mature sheep to a similar titre suggests that it may be possible to overcome the immunological hyporesponsiveness that may contribute to the disease susceptibility of young sheep.

Interaction between concanavalin A and vesicles or monolayers formed by fluorocarbon amphiphiles with sugar headgroups

Abstract Fluorocarbon amphiphiles with α-glucosyl units as headgroups can form stable vesicles and monolayers. Their vesicle agglutination occurs in the presence of concanavalin A (Con A), which can be reversed by addition of glucose. Monolayers derived from these amphiphiles are also significantly affected by Con A in the subphase. These results can be explained in terms of recognition between Con A and sugar headgroups of membrane-forming constituents. The agglutination is dependent upon headgroup composition, but independent of surface charges of the membranes.

Impairment of growth and immune function of avocet chicks from sites with elevated selenium, arsenic, and boron.

Avocets (Recurvirostra americana) hatched from eggs collected from the south Central Valley of California (USA) were studied to determine the impact of elevated concentrations of selenium, arsenic, and boron on the immune system and growth to maturity. Corcoran ponds were the reference site with low selenium (1.2 ppb) and arsenic (29 ppb) (boron not measured). Westfarmers Pond had elevated concentrations of selenium (319 ppb), arsenic (127 ppb), and boron (109 ppm). Pryse ponds also had elevated selenium, arsenic, and boron concentrations (13.9 ppb, 1,100 ppb, and 29.4 ppm, respectively). Size at hatch was significantly reduced (P < or = 0.05) in birds from Westfarmers and Pryse ponds. The growth rate was faster, but mean adult size was reduced in birds from Pryse ponds. Avocet chicks from Pryse and Westfarmers ponds exposed solely through in ovo transfer of these elements had significantly increased heterophil:lymphocyte ratios. The phagocytic activity of macrophages also was significantly reduced in these birds, and Pryse Pond birds had an increased proliferative ability of lymphocytes in the presence of concanavalin A, a T-cell mitogen. Avocet chicks (< or = 5 wk old) were captured from the various ponds and the same morphometric and immune function measurements made. The birds that were most severely impacted by exposure to these compounds were those that were collected from Pryse ponds.

Cellular Interactions of Murine Immune Cells Exposed to Live Mycobacterium intracellulare, Its Whole Lipid Extract, and Its Serovar-Specific Glycopeptidolipid

In this study we examined some of the immunological responses to Mycobacterium intracellulare and its lipid components. Our results indicate that infection with M. intracellulare can increase the expression of adhesion molecules, ICAM-1 and LFA-1, only at the site of injection (peritoneum). There was no change in the expression of these adhesion molecules in the lymphoid organs (thymus and spleen). Significant increases in the adhesion molecules were observed in the spleen cells incubated with the lipid derived from mycobacteria in the presence of concanavalin (Con A) compared to the Con A alone. The expression of the Thy 1.2 and Lyt-2 markers was not affected by the bacteria or their lipids. The results indicate a marked increase in the mitogenic response by the infected spleen cells removed at an early day. The blastogenic study also indicated that the lipids can reduce the mitogen-induced blastogenesis of spleen cells removed from M. intracellular- and saline-injected mice; moreover, they suggested that the spleen cells removed from Listeria monocytogens-infected mice can also be affected by mycobacterial lipids. This indicates a nonspecific effect by these lipids. The results that the immunological response was contingent upon prior exposure of the mice to M. intracellulare, and also was dependent on whether the cells came from the peritoneal cavity or lymphoid organs.

A technique for the isolation and purification of viable mucosal mast cells/globule leukocytes from the small intestine of parasitised sheep

A technique for the isolation and purification of viable mucosal mast cells/globule leukocytes from the small intestine of parasitised sheep. Internationaljournal for Parasitology24: 307–309. Romney sheep, 1–2 years old, immunized by at least three anthelmintic abbreviated infections of 80–100,000 Trichostrongylus colubriformis larvae usually produced high numbers of intestinal mucosal mast cells/globule leukocytes (MMC/GLs). In isolating these cells, the importance of maintaining the intestine at 37°C, removal of mucus with dithiothreitol, enzymatic dispersion and careful in vitro handling procedures for maximising cell viability are emphasised. The MMC/GLs were separated from most contaminant cells by using a Percoll discontinuous gradient. MMC/GLs collected at the |60/100 % Percoll interface were passed through a complement coated nylon wool column to remove the contaminating eosinophils. Viable MMC/GLs were able to grow in vitro in the presence of Concanavalin A and survive in culture for up to 30 days. The MMC/ GLs were readily identified by ultraviolet light microscopy after staining with auramine O.

Induction of T-Lymphocyte Adhesion by Histidine-Proline-Rich Glycoprotein and Concanavalin A

Histidine-proline-rich glycoprotein (HPRG) is a plasma protein which binds to a specific receptor on T-lymphocytes and represses T-cell activation and proliferation. In the presence of Concanavalin A (Con A). HPRG causes human T-lymphoblastic MOLT-3 cells and a fraction of normal human peripheral blood lymphocytes to attach to the culture dish and significantly change morphology by either extending processes or becoming elongated at the poles, respectively. HPRG and Con A are just as effective at inducing MOLT-3 attachment in a soluble or an immobilized form. MOLT-3 cell attachment is specific for HPRG, dose-dependent, and reversible in 72 hr. Only certain T-cell mitogenic lectins. Con A and phytohemagglutinin, are effective at stimulating adherence. Mannose, glucose, fucose, and N-acetylglucosamine inhibit HPRG-induced MOLT-3 cell attachment to different degrees, with methyl α-D-mannopyranoside being the most potent inhibitor. We propose that in vivo HPRG together with a naturally expressed lectin induces T-lymphocyte adhesion to initiate cell migration to sites of inflammation.

The presence of concanavalin A and canatoxin in Canavalia ensiformis DC tissue culture

Isolated embryos, cotyledons and embryos plusa fragment of cotyledon from seeds of Canavalia ensiformis (jack bean) were cultured in vitro. Concanavalin A and canatoxin cross-reactive material were detected by double immunodiffusion tests. Canatoxin was detectable until 30 days in cultures of embryos, embryos plus cotyledons and hypocotyls. Concanavalin A was also present in all cultures being detected until 90 days in cultures treated with 6-benzylaminopurine. No concanavalin A was detected in root cultures. Concanavalin A was present in cell suspensions until 45 days of culture; the culture medium contained neither concanavalin A nor canatoxin. Tissue cultures thus can produce Con A and CNTX and will be an important research tool for studying the biosynthesis of such substances.

Retrovirus infections in non-domestic felids: serological studies and attempts to isolate a lentivirus

An African lioness from the Zoo of Zurich had to be euthanized because of an inoperable tumor. The serum tested negative for feline leukemia virus (FeLV) p27 antigen by enzyme-linked immunosorbent assay (ELISA) but was strongly positive for feline immunodeficiency virus (FIV) antibodies by ELISA and Western blot. When her only offspring and mate were tested for FIV, high antibody titers to FIV were also found in their serum. Lymphocytes were prepared from these two lions on different occasions and co-cultivated with specific pathogen free (SPF) cat lymphocytes in the presence of concanavalin A and recombinant human interleukin-2 (IL-2) for 6 weeks. The cell culture supernatants tested negative for Mg 2+-dependent reverse transcriptase and FIV p24 by a double antibody sandwich ELISA throughout the culture period. Whole blood and buffy coat cells collected from these two lions were transmitted by intraperitoneal injection into two SPF cats. The two cats did not seroconvert for a period of 11 months nor could reverse transcriptase activity and FIV p24 antigen be demonstrated in the supernatant of several lymphocyte cultures. To determine the importance of lentivirus infections in zoo-kept wild felids, 124 serum samples were obtained from African lions, Indian and Siberian tigers, snow leopards, panthers, cheetahs and other wild cats from nine European zoos. In addition, serum samples collected from 12 Asiatic lions originating from Gir forest in the Indian State of Gujarat were included in this study. The sera were tested for antibodies to FIV, FeLV and feline syncytium-forming virus (FeSFV) by ELISA and Western blot using the respective viruses after gradient purification. In addition, some of the sera were also tested for antibodies to equine infectious anemia virus (EIAV) and Visna-Maedi virus (VMV). Antibodies to FIV were found in 30 53 (57%) of African lions, one of 18 tigers and one of four panthers. All other sera including those collected from the 12 Asiatic lions were negative for FIV antibodies. Some of the FIV positive lion sera had high antibody titers producing strong bands on Western blot strips even in dilutions of ⪢ 1 : 1000. The Western blot pattern of the lion sera differed from that of domestic cats in that primarily p24 and to a lesser degree p17 was recognized. Antibodies to FeSFV were found in 14 animals (seven with strong, seven with intermediate, reaction). No correlation was found between FIV and FeSFV infection. Antibodies to FeLV were found in two cheetahs which later turned out to have been vaccinated with Leukocell, a FeLV vaccine. Antibodies to EIAV (mainly p26) were found in most but not all of the FIV positive animals. In addition, six out of eight of the Asiatic lions tested had high antibody levels to EIAV p26. Antibodies to VMV p30 were mostly but not exclusively found in sera being positive also for EIAV. From these data it was concluded that a lentivirus antigenically closely related to FIV of domestic cats is widespread in wild felids kept in European zoos. Unsuccessful transmission experiments to SPF cats suggest that the lion virus is highly adapted to its host. Based on the high prevalence in African but not in Asiatic lions it may be postulated that this virus has its origins in Africa. Detection by Western blot of antibodies cross-reacting with EIAV in Asiatic lions seronegative for FIV indicates that there may exist an additional feline lentivirus not recognized so far.

Partial purification and characterization of chicken interleukin-2

Chicken interleukin 2 (IL-2) activity was partially purified from conditioned medium produced by culturing chicken splenic lymphocytes in the presence of concanavalin A. The purification procedure included sequential steps of gel filtration chromatography, reverse-phase high-pressure liquid chromatography, and phenyl-sepharose chromatography. Two peaks of IL-2 activity with apparent mol. wt. ranges of 36–39 kD and 17.5–25 kD were eluted from the Sephadex G100 gel filtration column. An increase in IL-2 spec. act. from 14 U mg −1 to between 2000 and 20 000 U mg −1 was obtained for the Sephadex G100 column peaks when subjected to the subsequent steps of the purification procedure. Alkylative reduction of the higher mol. wt. Sephadex G100 column peak (followed by re-chromatography with Sephadex G100), resulted in generation of the lower (17.5 kD) mol. wt. peak, indicating that chicken IL-2 is capable of either dimerizing or forming aggregates with other proteins. Elution of the lower mol. wt. IL-2 activity from a non-reducing sodium dodecyl sulfatepolyacrylamide gel demonstrated an apparent mol. wt. for chicken IL-2 of 20 kD, which confirmed the range of 17.5–25 kD seen with gel filtration.

Promotion of lymphocyte blastogenesis by hemodialysate of chronic renal failure.

Effects of hemodialysate of patients with chronic renal failure (CRF) on blastogenesis of human peripheral blood lymphocytes in the presence of concanavalin A or phytohemagglutinin was investigated. Hemodialysates from 11 CRF patients significantly promoted lymphocyte blastogenesis when compared with control dialysis fluids (p less than 0.01). The strongest activity (39% promotion of the lymphocyte blastogenesis) was observed with a hemodialysate obtained at 0.5 h after beginning dialysis. The activity decreased thereafter. On the contrary, the blastogenesis-promoting activity in plasma decreased significantly after hemodialysis (p less than 0.01, n = 11). To further confirm the presence of low-molecular-weight factor(s) in CRF, ultrafiltration of plasma obtained from CRF and healthy subjects was conducted using a membrane filter with a molecular cutoff of 3,000 D. The filtrate of CRF plasma significantly promoted lymphocyte blastogenesis when compared to that of healthy subjects (p less than 0.01). Heat treatment (100 degrees C, 40 min) did not abolish the activity of the hemodialysate. None of the drugs taken by the patients nor creatinine accumulated in CRF promoted the lymphocyte blastogenesis. Chromatographic analysis of a hemodialysate demonstrated several peaks which were absent in the control dialysis fluid. These results showed the presence of a novel lymphocyte-stimulating factor(s) in CRF, which is heat stable and has a low molecular weight (less than 3,000 D).