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PubMed1980

Effect of dextran-S (alpha, 1-3 dextran) on the growth of plasmacytomas MOPC-104E and J558.

The murine plasmacytomas MOPC-104E and J558 secrete IgM-lambda and IgA-lambda, respectively, which are antibodies to alpha, 1-3 dextran, a constituent of dextran-S (DEX-S) extracted from Leuconostoc mesenteroides. A single i.p. injection of 10 microgram DEX-S into BALB/c mice from 7 days before and up to 3 days after the implantation of 5 x 10(3) plasmacytoma cells protected the BALB/c mice from developing the tumors. Immunization with other antigens, such as Escherichia coli lipopolysaccharide, inulin (alpha, 1-6 linkage), and dextran T-10 (no known alpha, 1-3 linkages) did not protect the mice from developing the tumors. Growth of LPC-1 was not affected by DEX-S. The mechanism of this growth inhibition is unknown. It does not appear to depend solely on binding of antigen to tumor cells, and the limits of the effective time intervals between antigen and tumor injection suggest dependence on the presence of antibody to alpha-1,3 dextran.

Animals↗

PubMed1983

Antigen size and charge in immune complex glomerulonephritis. II. Passive induction of immune deposits with dextran-anti-dextran immune complexes.

Utilizing dextrans of restricted sizes (10,000, 70,000, 500,000 daltons), modified with regard to charge (neutral, polycationic, polyanionic) and an anti-dextran murine IgA myeloma, W3129, the authors have examined a model that may be used in the study of the combined effect of size and charge on renal deposition of immune complexes. Polycationic DEAE dextran complexes, using the 10,000 dalton antigen, showed a mesangiocapillary pattern of deposition. The other antigens showed focal to diffuse mesangial localization of varying degree. This indicates the potential usefulness of this system in examining the factors important in glomerular immune injury. The relevance to other observations, importance of polysaccharide antigens, and role in circulating versus in situ or "planted" immune complex models are considered.

Animals↗

PubMed1996

Effects of fused tryptophan rich peptides to a recombinant protein. A domain on the partitioning in polyethylene glycol-dextran and Ucon-dextran aqueous two-phase systems.

Genetic engineering has been used to construct fusion proteins with tryptophan containing peptides. The peptides and the fusion proteins have been partitioned in aqueous two-phase systems of poly(ethylene glycol) (PEG)-dextran and Ucon-dextran. The studied model protein was ZZT0, where Z is an engineered domain of domain B of staphylococcal protein A. The specially designed hydrophobic peptides, Ala-Trp-Trp-Pro (T1) and (Ala-Trp-Trp-Pro)2 (T2), have been inserted into ZZT0, to give the peptide-protein fusions ZZT1 and ZZT2. In the experimental studies it was found that T1 and T2 preferred the PEG phase and even more the Ucon phase over the dextran phase. For T2 the partitioning was more one sided than for T1. For the fusion proteins, ZZT1 and ZZT2, the partitioning was enhanced into the PEG or Ucon rich phase as compared to ZZT0. The effects were lower than expected from independent contributions to the partition coefficient from the protein and the peptides. A heterogeneous lattice model was used to calculate theoretical peptide and protein partition coefficients. The calculations could reproduce the qualitative features of the experimental data. The model results suggest that a part of these experimentally observed effects is due to a depletion zone, i.e. a zone of reduced polymer concentration around the protein. The experimental results indicate a further reduction of the partition coefficient, beyond that predicted by the lattice calculations. A possible folding of the inserted peptide is discussed as a plausible mechanism for this further reduction in the partition coefficient.

Dextrans↗

PubMed2006

Dextran 40 (Rheomacrodex) or Polygeline (Haemaccel) as an epidural patch for post dural puncture headache: a neurotoxicity study in a rat model of Dextran 40 and Polygeline injected intrathecally.

BACKGROUND AND OBJECTIVE: Although an epidural autologous blood patch is considered the most effective treatment for post dural puncture headache, which sometimes occurs following spinal or inadvertent spinal anaesthesia, there remains a need for alternative materials for epidural patches. We investigated the potential neurotoxicity of Dextran 40 (Rheomacrodex) and Polygeline (Haemaccel) used for this purpose in a rat model. METHODS: Repeated boluses of 10% Dextran 40, 3.5% Polygeline or 0.9% saline were injected intrathecally over a period of 1 month in three groups of rats. RESULTS: No behavioural or clinical derangements were observed in any of the three groups during this period. After sacrifice of the animals at the end of the experiment, no significant differences in the histopathological appearances of the spinal cords in the three groups were observed. No toxic effects diminishing viability of spinal cord cells were evident. Similarly, viability of renal, hepatic and peripheral blood mononuclear cells remained unaffected (98% +/- 2%). CONCLUSIONS: No deleterious effects, clinical or cellular, were evident in this rat model when Dextran 40 or Polygeline were injected intrathecally. Thus, both substances can be considered as possible alternative materials for epidural patches.

Animals↗

PubMed2000

Natural killer cell-dependent immunoglobulin G2a anti-bovine serum albumin (BSA) response elicited by high molecular weight dextran-BSA conjugates associated with dextran-mediated macrophage-natural killer cell interaction.

The roles of the interferon-gamma (IFN-gamma) and interleukin-12 (IL-12) produced during natural killer (NK) cell interaction with macrophages (M phi) were investigated as the basis for the induction of immunoglobulin G2a (IgG2a) anti-bovine serum albumin (BSA) responses by high molecular weight dextran conjugated to BSA (HMW-DEX-BSA). BALB/c mice immunized with HMW-DEX-BSA produced significantly higher levels of both IgG1 and IgG2a anti-BSA than did mice immunized with BSA alone. Both IgG1 and IgG2a anti-BSA levels were higher in mice immunized with BSA conjugated to dextran of molecular weight (MW) 5 000 000-40 000 000 compared with dextran of MW 10,000-60,000. The enhancement of anti-BSA IgG2a levels but not of anti-BSA IgG1 levels was inhibited when free BSA was added to the HMW-DEX-BSA conjugate. NK cell depletion during HMW-DEX-BSA immunization of mice resulted in significantly lower anti-BSA IgG2a levels without affecting anti-BSA IgG1 levels. Naive splenocytes or M phi + NK cell co-cultures incubated with HMW-DEX or HMW-DEX-BSA produced higher IFN-gamma levels than splenocytes or co-cultures incubated with BSA alone. HMW-DEX stimulated both IFN-gamma and IL-12 production by M phi + NK cell co-cultures in a dose-dependent manner. DEX-induced IFN-gamma production by NK cells was dependent upon the presence of IL-12, and IL-12 production by M phi was dependent upon the presence of IFN-gamma in these co-cultures. Both M phi and NK cells bound DEX to their surfaces. These data demonstrate that BSA linked to HMW-DEX enhanced both T-helper-1- and T-helper-2-associated antibody responses to BSA. The results also indicate an IL-12-dependent positive feedback interaction between NK cells and M phi that supports a NK cell/IFN-gamma-dependent mechanism for enhancement of anti-BSA IgG2a antibody responses in mice immunized with HMW-DEX-BSA protein conjugates.

Adjuvants, Immunologic↗

PubMed1973

Immunochemical analysis of the cross-reacting idiotypes of mouse myeloma proteins with anti-dextran activity and normal anti-dextran antibody.

The idiotype of the mouse myeloma protein with anti-alpha-1,3 dextran activity, J558, has been characterized by a solid-phase radioimmunoassay. The idiotype of the J558 protein depends on a specific light and heavy chain interaction and is altered in the presence of the hapten, nigerose. Cross-reacting idiotypes were found on another mouse myeloma protein with alpha1,3 dextran specificity, normal anti-dextran antibody, and certain reconstructed myeloma proteins composed of the J558 heavy chain and heterologous light chains.

Amino Acid Sequence↗

PubMed1980

Immunochemical studies on dextrans. Two distinct alpha 1 linked to 3 specificities of rabbit anti-dextran B1355.

Rabbit anti-dextran B1355 sera prepared by injecting rabbits with Leuconostoc mesenteroides NRRL B1355 were separated on a Sephadex G75 column into two fractions, one binding and the other not binding to the column. Oligosaccharide inhibition of precipitation of the two fractions with dextran B1355 indicated that both fractions had alpha 1 linked to 3 specificity. However, antibodies in the non-binding fraction were shown to be directed against O-alpha-D-glucopyranosyl-(1 linked to 3)-O-alpha-D-glucopyranosyl-(1 linked to 6)-D-glucose, while those in the binding fraction were directed against O-alpha-D-glucopyranosyl-(1 linked to 6)-O-alpha-D-glucopyranosyl-(1 linked to 3)-D-glucose. These results are consistent with the proposal of Bhoopalam et al. (Proc. Soc. Exp. Biol. Med. (1979(=) 161, 430-434) that there are different epitopic groups on this dextran.

Animals↗

PubMed2000

Self-complex formation of nicotinamide-modified dextran with carboxymethyl dextran using their degradation products.

A pseudo-metabolic cycle as a self-degradation system was designed: enzymatic degradation products from a polysaccharide generate oxidants which introduce a cationic charge into the polysaccharide chains, and can form a polyion complex with an anionic polysaccharide. As a component of such a system, dextran, with various degrees of nicotinamide substitution, was prepared. Its degradation by dextranase, redox reaction via glucose oxidase-catalysis, and polyion complex formation with carboxymetyl dextran (CMD) were examined. Nicotinamide-modified dextran (NA-Dex) with nine nicotinamide moieties per 100 glucose units was soluble in PBS and completely oxidized by > 100 mM H2O2. The oxidized type of NA-Dex was found to form a 1:1 complex with CMD. By the addition of dextranase, isomaltase, and glucose oxidase (GOD) to phosphate buffer solution of the reduced type of NA-Dex and CMD, the transmittance of the solution dropped, suggesting polyion complex formation via the oxidation of 1,4-dihydronicotinamide in NA-Dex by H2O2 generated from GOD-catalytic reaction. These findings are of great importance for designing a self-complex formation system aimed at biodegradable and osillative drug release.

Biocompatible Materials↗

PubMed2000

Surface modification of polystyrene nanoparticles using dextrans and dextran-POE copolymers: polymer adsorption and colloidal characterization.

Hydrophobically-modified dextran (dextran-phenoxy, DexP) and dextran-phenoxy-poly(oxyethylene) (DexP-POE) copolymers have been used to modify the surface properties and the stability of polystyrene nanoparticles. We examined the effect of phenoxy group and POE chain concentrations on their adsorption behaviour. The adsorbed amount was determined by the standard depletion method and the layer thickness of the adsorbed layer by photon correlation spectroscopy and electrokinetic measurements. The results show that the hydrophobic interaction is the driving force during the adsorption while the layer thickness correlates with the interfacial concentration of grafted POE chains. The effects of adsorbed layers on the properties of latex dispersions have been characterized in terms of the stability of the dispersions toward added electrolyte and temperature. The conformation of the adsorbed copolymers is discussed in relation to layer thickness and colloidal stability of suspensions.

Adsorption↗

PubMed1975

Interactions of the third component of complement (C3) with cross-linked dextran. IV. Adherence of lymphocytes to C3 coated dextran gel particles.

In previous studies we could show that the third component of complement (C3) is bound from normal serum to cross-linked dextran (Sephadex) after activation via an alternate pathway. Data presented in this paper demonstrate that a subpopulation of human lymphocytes adheries to C3 coated Sephadex particles. The adhering subpopulation of lymphocytes is identical with or overlaps extensively with lymphocytes bearing easily detectable membrane Ig. This phenomenon can be used for the fractionation of lymphocyte subpopulations. After a single passage of tonsillar lymphocytes through C3 coated Sephadex bead columns, no membrane Ig positive lymphocytes were detectable in the effluent. 97-100% of effluent cells formed rosettes with untreated sheep red blood cells, thus resembling pure T cells. Apart from that, the use of C3 coated dextran gel particles allows also the recovery of adherent cells after dextranase digestion of the dextran gel particles. An investigation of retained cells showed enrichment of B cells, but also T cells were demonstrable. The retention of these T cells is probably due to nonspecific interactions.

Cell Separation↗

PubMed1975

Interactions of the third component of complement (C3) with cross-linked dextran. II. Demonstration of an alternate pathway activation as binding mechanism of C3 to cross-linked dextran.

In previous investigations we could show that incubation of cross-linked dextran (Sephadex) with normal human serum results in the binding of the third component of complement to the Sephadex beads. In this paper, data are presented which demonstrate that not only human but also guinea pig C3 reacts with Sephadex and that this binding is due to an alternate pathway of C3 activation. This conclusion was drawn, since a) C3 is bound also from guinea pig serum with total deficiency of C4, b) the reaction can be completely blocked by EDTA but only diminished by EGTA and c) the reaction turned out to be temperature dependent with an optimum at 37 degrees C and could be abolished by diluting the serum more than 1:16. The ability of cross-linked dextran to activate C3 via the alternate pathway seems to be due to conformational changes, since in our experiments soluble dextran of the same source was found to be ineffective in this respect. Implications from these findings and possible applications are discussed.

Animals↗

PubMed1992

Systemic and regional oxygen uptake and lactate flux in endotoxic dogs resuscitated with dextran and dopexamine or dextran alone.

We examined how volume resuscitation with and without dopexamine, a potent beta 2-adrenergic and dopaminergic agonist, would affect O2 uptake (VO2), O2 delivery (DO2), and lactate metabolism in whole body, skeletal muscle, and gut of 18 anesthetized dogs after they were infused for 1 hr with 2 mg/kg endotoxin. Six dogs were then infused with dextran for 2 hr at 0.5 ml/kg/min (DEX); another six were given the same volume with 12 micrograms/kg/min dopexamine (DPX); and a third group received no treatment (NT). After endotoxin, all animals were hypotensive; cardiac output decreased 30%; and DO2 to whole body, skeletal muscle, and gut were at or below critical for VO2. DO2 was raised above critical in whole body and gut of DEX and DPX but not in muscle of DPX, which produced lactate. Whole body DO2 approached preendotoxin level by 2 hr in DEX and DPX but stayed near critical in NT. At that time, gut VO2 was higher in DPX than in DEX or NT, and lactate efflux became less than in DEX. Vascular reactivity was present in the gut at the end of the experiment in six of six DPX studies, in four of six DEX studies, and in none of the NT studies. These results suggest that resuscitation with dopexamine + dextran after induction of endotoxic shock may be more beneficial than dextran alone, particularly for the gut mucosa.

Animals↗

PubMed1975

Influence of molecular structure on the tolerogenicity of bacterial dextrans. I. The alpha1--6-linked epitope of dextran B512.

Native dextran B512 is a near-linear glucose polymer with 96 per cent alpha1--6 and 4 per cent alpha1--3 linkages and a molecular weight (mol. wt) of 8 X 10(7). Sheep RBC sensitized with its O-stearoyl derivative (prepared by a modified method) have been used satisfactorily in direct PFC assays. B512 immunizes BALB/c mice optimally with doses of 1--10 mug and produces B-cell tolerance with 1 mg upwards. The specificity of the response determined by PFC inhibition analysis, is directed towards an alpha1--6-linked epitope. High dose tolerance is not preceded by immunity and is stable on cell transfer to irradiated recipients in which responsiveness becomes perceptible after 4--6 weeks. Progressive depolymerization of this polysaccharide reduces immunogenicity and tolerogenicity, both of which are extinguished when the mol. wt falls to 2 X 10(4). Optimal immunization with B512 is succeeded by partial tolerance (previously characterized by analogous levan experiments as a B-cell exhaustion process). The tolerance threshold dose of B512 is reduced 1000-fold during immunosuppression with cyclophosphamide. PFC inhibition studies supported the contention that tolerogenicity of polysaccharides is influenced by their overall binding capacities. A direct relationship between inhibitory and tolerogenic activities was found both with B512 fractions of varying mol. wt and with heterologous dextrans. The similarities between B512 and levan argue against the association of a highly branched structure with greater tolerogenicity. The effect of reducing the percentage of alpha1--6 linkages in dextrans suggests, however, that epitope density probably plays a contributory role in determining the outcome of interaction between polysaccharides and B cells.

Animals↗

PubMed2006

Dextran sodium sulfate strongly promotes colorectal carcinogenesis in Apc(Min/+) mice: inflammatory stimuli by dextran sodium sulfate results in development of multiple colonic neoplasms.

The mouse model for familial adenomatous polyposis, Apc(Min/+) mouse, contains a truncating mutation in the Apc gene and spontaneously develops numerous adenomas in the small intestine but few in the large bowel. Our study investigated whether dextran sodium sulfate (DSS) treatment promotes the development of colonic neoplasms in Apc(Min/+) mice. Apc(Min/+) and Apc+/+ mice of both sexes were exposed to 2% dextran sodium sulfate in drinking water for 7 days, followed by no further treatment for 4 weeks. Immunohistochemistry for cyclooxygenase-2, inducible nitric oxide synthase, beta-catenin, p53, and nitrotyrosine, and mutations of beta-catenin and K-ras and loss of wild-type allele of the Apc gene in the colonic lesions were examined. Sequential observation of female Apc(Min/+) mice that received DSS was also performed up to week 5. At week 5, numerous colonic neoplasms developed in male and female Apc(Min/+) mice but did not develop in Apc+/+ mice. Adenocarcinomas developed in Apc(Min/+) mice that received DSS showed loss of heterozygosity of Apc and no mutations in the beta-catenin and K-ras genes. The treatment also significantly increased the number of small intestinal polyps. Sequential observation revealed increase in the incidences of colonic neoplasms and dysplastic crypts in female Apc(Min/+) mice given DSS. DSS treatment increased inflammation scores, associated with high intensity staining of beta-catenin, cyclooxygenase-2, inducible nitric oxide synthase and nitrotyrosine. Interestingly, strong nuclear staining of p53 was specifically observed in colonic lesions of Apc(Min/+) mice treated with DSS. Our results suggest a strong promotion effect of DSS in the intestinal carcinogenesis of Apc(Min/+) mice. The findings also suggest that strong oxidative/nitrosative stress caused by DSS-induced inflammation may contribute to the colonic neoplasms development.

Adenocarcinoma↗

PubMed1984

Effectiveness of normal saline solution, dextran 40 or dextran 75, and aprotinin (Trasylol) on renal blood flow preservation during acute canine pancreatitis.

A decrease in renal blood flow is believed to be important in the genesis of the acute renal failure of acute pancreatitis. In some instances, this decrease is undoubtedly due to hypovolemia, whereas in other instances, a circulating vasotoxic agent, possibly trypsin, has been incriminated. Using a canine model of pancreatitis induced by retrograde injection of bile along the pancreatic duct, the effects on renal blood flow of correcting the hypovolemia or administering aprotinin (a trypsin inhibitor) were studied using externally applied flow probes. Correcting the hypovolemia with N saline solution had no effect; the renal blood flow continued to decrease (p less than 0.05). When dextran 40 or dextran 75 was employed, the decrease in renal blood flow was prevented. After the administration of aprotinin, the renal blood flow actually increased (p less than 0.025) compared with preadministration values. It appears that aprotinin may have played a role in preventing this serious complication of pancreatitis.

Acute Disease↗

PubMed1987

Apparent endocytosis of fluorescein isothiocyanate-conjugated dextran by Saccharomyces cerevisiae reflects uptake of low molecular weight impurities, not dextran.

Concurrent with Riezman's report (Riezman, H. 1985, Cell. 40:1001-1009) that fluid-phase endocytosis of the small molecule Lucifer yellow occurs in the yeast Saccharomyces cerevisiae, Makarow (Makarow, M. 1985. EMBO [Eur. Mol. Biol. Organ.] J. 4:1861-1866) reported the endocytotic uptake of 70-kD FITC-dextran (FD) and its subsequent compartmentation into the yeast vacuole. Samples of FD synthesized and purified here failed to label yeast vacuoles under conditions that allowed labeling using commercial FD. Chromatography revealed that the commercial FD was heavily contaminated with at least three low molecular weight fluorescent compounds. Dialysis was ineffective for removing the contaminants. After purification (Sephadex G25, ethanol extraction), commercial FD was incapable of labeling vacuoles. Extracts of cells labeled with partially purified FD contained FITC, not FD, based on Sephadex and thin layer chromatography. In either the presence or absence of unlabeled 70-kD dextran, authentic FITC (10 micrograms/ml) was an effective labeling agent for vacuoles. The rapid kinetics (0.28 pmol/min per 10(6) cells at pH 5.5) and the pH dependence of FITC uptake suggest that the mechanism of FITC uptake involves diffusion rather than endocytosis. In view of these results, labeling experiments that use unpurified commercial FD should be interpreted with caution.

Antigens↗

PubMed1998

[Influence of dextran 40 and dextran 70 on the adhesion of erythrocytes to endothelial cells].

Adopting the flow chamber realtime microrecordation system, we studied the dynamic effects of dextran 40(DX40) and dextran 70(DX70) on the adhesion of erythrocytes to monolayer of cultured human umbilical vein endothelial cells (HUVEC). The results demonstrated that erytherocytes pretreated with DX40 adhered to HUVEC less than the erythrocytes of the control group did, but DX70 increased the number of erythrocytes adhering to HUVEC. The higher the concentration of DX70 was, the more the erythrocytes pretreated with DX70 adhered to HUVEC. When shear stress increased, the decrease rate of the number of erythrocytes (pretreated with DX70) adhering to HUVEC declined with the increase of DX70 concentration. These indicate that DX40 as an expander of blood plasma is better than DX70.

Cell Adhesion↗

PubMed1975

Influence of molecular structure of the tolerogenicity of bacterial dextrans. III. Dissociation between tolerance and immunity to the alpha1--6- and alpha1--3-linked epitopes of dextran B1355.

Dextran B1355 induces a direct PFC response detectable with dextran B512-sensitized red cells which is directed towards an alpha1--6-linked glucose epitope. This response is distinguishable from the alpha1--3-linked specificity assayed by homologous sensitization in that: (a) it is totally suppressed in donors previously rendered tolerant of B512; (b) the PFC are sensitive to inhibition by B512 and isomaltohexaose. The alpha1--6 epitope of B1355 is less immunogenic in BALB/c mice than that with alpha1--3 linkage, inducing a lower amplitude of response and requiring a 100-fold greater minimal dose, while conversely, it is the more effective tolerogen. No alpha1--6-specific response develops in 50 per cent of mice given 10 mg of B1355 and all become totally unresponsive within 14 days. This tolerant state remains stable when spleen cells are transferred to irradiated recipients. By comparison, parallel depression of the alpha1--3 response is not great and rapidly lost by similar transfer. No correlation was observed between the levels of alpha1--6 suppression and alpha1--3 response induced by 10 mg of B1355 in individual mice. The dissociative aspects of the responses to these two epitopes present on the same molecule are discussed in relation to some current theories of B-cell tolerance induction. It is argued that the present findings are contrary to those models which attribute a causal role to mitogenic overstimulation or failure to generate an extrinsic 'second signal'.

Animals↗