Evidence for a relationship between chloroquine and complement from studies with lymphocyte mitogens: possible implications for the mechanism of action of chloroquine in disease

1975 ◽  
Vol 21 (10) ◽  
pp. 1581-1586 ◽  
Author(s):  
D. R. Forsdyke
Keyword(s):  
Autoimmune Disease ◽  
Mechanism Of Action ◽  
Concanavalin A ◽  
Time Course ◽  
Con A ◽  
Therapeutic Value ◽  
Dependent Inhibition ◽  
High Concentrations

Chloroquine increases the inhibition of cultured lymphocytes by high concentrations of phytohemagglutinin (PHA) or concanavalin A (Con A). The inhibition is also increased by complement. Thus chloroquine and complement have similar effects. Time-course studies show that chloroquine increases the rate of onset of the complement-dependent inhibition. In serum preheated to inactivate complement, chloroquine can partially simulate the effect of complement. It is suggested that at certain stages in malaria or autoimmune disease the rate of clearance of parasitized erythrocytes or autoreactive lymphocytes is limited by the concentration of complement. Under these conditions a drug such as chloroquine, which could enhance or simulate the action of complement, might be of therapeutic value.

scholarly journals The effect of concanavalin A on the rat electro-olfactogram at various odorant concentrations

1987 ◽  
Vol 245 (1) ◽  
pp. 185-189 ◽  
Author(s):  
S G Shirley ◽  
E H Polak ◽  
D A Edwards ◽  
M A Wood ◽  
G H Dodd
Keyword(s):  
Concentration Dependence ◽  
Concanavalin A ◽  
Olfactory Receptor ◽  
Dissociation Constants ◽  
Con A ◽  
Odour Concentration ◽  
High Concentrations

We have studied the effect of concanavalin A (Con A) on the rat electro-olfactogram response to several odorants. Each odorant was applied over a range of concentrations. For hydrophobic odorants whose response was affected by Con A, the diminution in response was maximal at odorant concentrations of about 1 microM in the olfactory mucus. The (odour) concentration-dependence of the change is compatible with the idea that Con A inactivates one or more types of olfactory receptor that normally bind odorants with dissociation constants of the order of 100 nM. With hydrophilic odorants we had to apply concentrations very much higher than this to elicit any response from the system. At these high concentrations we could observe Con A-induced diminutions in response.

Cetyltrimethylammonium bromide (CTAB) promote amyloid fibril formation in carbohydrate binding protein (concanavalin A) at physiological pH

RSC Advances ◽  
2016 ◽  
Vol 6 (44) ◽  
pp. 38100-38111 ◽  
Author(s):  
Javed Masood Khan ◽  
Mohd Shahnawaz Khan ◽  
Mohd Sajid Ali ◽  
Nasser Abdulatif Al-Shabib ◽  
Rizwan Hasan Khan
Keyword(s):  
Concanavalin A ◽  
Cetyltrimethylammonium Bromide ◽  
Amyloid Fibril ◽  
Alpha Helix ◽  
Fibril Formation ◽  
Carbohydrate Binding ◽  
Con A ◽  
Amyloid Fibril Formation ◽  
High Concentrations ◽  
Β Sheet

Low concentration of CTAB provoked cross β-sheet formation whereas high concentrations of CTAB direct to alpha helix induction in Con A.

Immunomodulatory Effect of Fu-Fang-Tai-Pan-Pian, a Traditional Chinese Tonic Medicine

1994 ◽  
Vol 22 (02) ◽  
pp. 147-153 ◽  
Author(s):  
G.A. Boissonneault ◽  
S. Mohapatra ◽  
H. Cai
Keyword(s):  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Mechanism Of Action ◽  
Concanavalin A ◽  
Con A ◽  
Organic Extract ◽  
Relative Ability ◽  
Organic Extracts ◽  
Chloroform Methanol ◽  
Insight Into

The purpose of this study was to evaluate the effect of the traditional Chinese medicine Fu-Fang-Tai-Pian-Pian on responsiveness of mouse spleen leukocytes to the mitogens concanavalin A (con A), phytohemrnaglutinin (PHA), and bacterial endotoxin (LPS). Aqueous and chloroform/methanol extracts of the drug were prepared and added to mitogen-stimulated cultures at doses ranging from 0.625% to 20% by volume. The aqueous extract depressed responsiveness to all mitogens at all doses tested, and was significantly more potent in this regard than the organic extract. The organic extract depressed responsiveness at low dilutions; however it significantly stimulated responsiveness to PHA and LPS, but not to con A, at dilutions. of 2.5% or less. The relative ability of compounds partitioning into aqueous and organic extracts of the medicinal mixture to both stimulate and depress the ability of lymphocytes to proliferate may provide insight into the mechanism of action of this and related medicines.

Role of concanavalin A as an endocytic modulator in Chinese hamster ovary cells

1981 ◽  
Vol 50 (1) ◽  
pp. 135-147
Author(s):  
B. Storrie ◽  
K.M. Maurey
Keyword(s):  
Concanavalin A ◽  
Chinese Hamster Ovary ◽  
Cho Cells ◽  
Chinese Hamster Ovary Cells ◽  
Chinese Hamster ◽  
Con A ◽  
Ovary Cells ◽  
Fibroblast Line ◽  
High Concentrations ◽  
Secondary Lysosomes

The effect of the lectin, concanavalin A (Con A), on pinocytic uptake and pinosome-lysosome fusion in Chinese hamster ovary (CHO) cells, a fibroblast line, was investigated. The glycosylated protein, horseradish peroxidase (HRPase), and the non-glycosylated protein, 125I-labelled bovine serum albumin ([125I]BSA), was used as endocytic tracers. Con A at high concentrations (greater than or equal to 50 micrograms/ml) promoted the uptake of HRPase and inhibited the degradation of ingested HRPase. Con A inhibited the degradation of HRPase whether the two were added simultaneously or at different times to the cultures. Fusion of HRPase-positive pinosomes with secondary lysosomes was observed by electron microscopy in Con A-treated CHO cells. Con A at 200 micrograms/ml had no effect on either the uptake or degradation of [125I]BSA. Together these observations strongly suggest that the effects of high Con A concentrations on the uptake and degradation of HRPase are a consequence of direct complex formation between lectin and glycoprotein. Con A does not appear to have a general modulating effect on the dynamics of endocytic membrane in CHO cells.

Concanavalin A-induced Aggregation of Human Blood Platelets

1975 ◽  
Vol 33 (02) ◽  
pp. 354-360 ◽  
Author(s):  
Heinrich Patscheke ◽  
Reinhard Brossmer
Keyword(s):  
Concanavalin A ◽  
Binding Capacity ◽  
Specific Binding ◽  
Blood Platelets ◽  
Residual Effect ◽  
Independent Effect ◽  
Con A ◽  
Experimental Conditions ◽  
Main Effect ◽  
Induced Aggregation

SummaryConcanavalin A (CON A) causes platelets to aggregate. A Ca++-independent effect of CON A could be separated from a main effect which depends on Ca++. The main effect probably is a consequence of the CON A-induced platelet release reaction and therefore is platelet-specific. The weak residual effect observed in the presence of Na2EDTA may be due to a similar mechanism as has been demonstrated for CON A-induced aggregations of several other normal and malignant transformed animal cells.Na2EDTA did not inhibit the carbohydrate-specific binding capacity of CON A. Therefore, Na2EDTA appears not to demineralize the CON A molecules under these experimental conditions.α-methyl-D-glucoside inhibits the Ca++-independent as well as the Ca++-dependent effect of CON A.Pretreatment by neuraminidase stimulated the platelet aggregation induced by CON A. It is possible that removal of terminal sialic acid residues makes additional receptors accessible for the binding of CON A.

High concentrations of oxygen modulate in vitro Con A responses of rat lymphoid cells. Effect of 2-mercaptoethanol

1985 ◽  
Vol 11 (1) ◽  
pp. 51-55 ◽  
Author(s):  
Laurence Kraus ◽  
Philippe Lacombe ◽  
Michel Fay ◽  
Jean-Jacques Pocidalo
Keyword(s):  
Lymphoid Cells ◽  
Con A ◽  
High Concentrations

scholarly journals The role of interleukin 12 and nitric oxide in the development of spontaneous autoimmune disease in MRL/MP-lpr/lpr mice.

1996 ◽  
Vol 183 (4) ◽  
pp. 1447-1459 ◽  
Author(s):  
F P Huang ◽  
G J Feng ◽  
G Lindop ◽  
D I Stott ◽  
F Y Liew
Keyword(s):  
Nitric Oxide ◽  
Autoimmune Disease ◽  
Cultured Cells ◽  
Daily Injection ◽  
Interleukin 12 ◽  
No Production ◽  
Necrosis Factor Alpha ◽  
Ifn Gamma ◽  
Peritoneal Cells ◽  
High Concentrations

MRL/MP-lpr/lpr (MRL/lpr) mice develop a spontaneous autoimmune disease. Serum from these mice contained significantly higher concentrations of nitrite/nitrate than serum from age-matched control MRL/MP-+/+ (MRL/+), BALB/c or CBA/6J mice. Spleen and peritoneal cells from MRL/lpr mice also produced significantly more nitric oxide (NO) than those from the control mice when cultured with interferon (IFN) gamma and lipopolysaccharide (LPS) in vitro. It is interesting to note that peritoneal cells from MRL/lpr mice also produced markedly higher concentrations of interleukin (IL) 12 than those from MRL/+ or BALB/c mice when cultured with same stimuli. It is striking that cells from MRL/lpr mice produced high concentrations of NO when cultured cells from MRL/+ or BALB/c mice. The enhanced NO synthesis induced by IFN-gamma/LPS was substantially inhibited by anti-IL-12 antibody. In addition, IL-12-induced NO production can also be markedly inhibited by anti-IFN-gamma antibody, but only weakly inhibited by anti-tumor necrosis factor alpha antibody. The effect of IL-12 on NO production was dependent on the presence of natural killer and possibly T cells. Serum from MRL/lpr mice contained significantly higher concentrations of IL-12 compared with those of MRL/+ or BALB/c control mice. Daily injection of recombinant IL-12 led to increased serum levels of IFN-gamma and NO metabolites, and accelerated glomerulonephritis in the young MRL/lpr mice (but not in the MRL/+ mice) compared with controls injected with phosphate-buffered saline alone. These data, together with previous finding that NO synthase inhibitors can ameliorate autoimmune disease in MRL/lpr mice, suggest that high capacity of such mice to produce IL-12 and their greater responsiveness to IL-12, leading to the production of high concentrations of NO, are important factors in this spontaneous model of autoimmune disease.

scholarly journals Visualization of intracellular concanavalin A binding sites in retinal photoreceptors.

1978 ◽  
Vol 26 (10) ◽  
pp. 822-828 ◽  
Author(s):  
I Nir
Keyword(s):  
Concanavalin A ◽  
Binding Sites ◽  
Photoreceptor Cells ◽  
Con A ◽  
Thin Sections ◽  
Glycol Methacrylate ◽  
Outer Segments ◽  
Retinal Photoreceptors ◽  
Carbohydrate Components ◽  
The Relationship

Localization of carbohydrate components in retinal photoreceptor cells and membranes was studied. Frog and rat retinas were fixed with glutaraldehyde and embedded in glycol methacrylate or in a mixture of glycol methacrylate, glutaraldehyde and urea. Thin sections were incubated with ferritin-labeled concanavalin A (F-Con A) and stained with osmium vapors. Intensive binding was observed in both rod and cone outer segments. In the rod inner segment, differential binding of F-Con A was demonstrated. While numerous ferritin granules were observed in the myoid zone, only a few were seen in the ellipsoid zone, except for a local accumulation along the plasma membrane. In the rod outer segment, Con A binding sites were closely associated with the disk membranes. Ferritin granules were observed on both sides of the membranes. The relationship between the localization of Con A binding sites and the orientation of visual pigment molecules within the rod outer segments disk membranes was discussed.

scholarly journals Therapeutic Value of Single Nucleotide Polymorphisms on the Efficacy of New Therapies in Patients with Multiple Sclerosis

2021 ◽  
Vol 11 (5) ◽  
pp. 335
Author(s):  
María José Zarzuelo Romero ◽  
Cristina Pérez Ramírez ◽  
María Isabel Carrasco Campos ◽  
Almudena Sánchez Martín ◽  
Miguel Ángel Calleja Hernández ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Mechanism Of Action ◽  
Dimethyl Fumarate ◽  
Response To Treatment ◽  
Nucleotide Polymorphisms ◽  
New Therapies ◽  
Therapeutic Value ◽  
The Impact

The introduction of new therapies for the treatment of multiple sclerosis (MS) is a very recent phenomenon and little is known of their mechanism of action. Moreover, the response is subject to interindividual variability and may be affected by genetic factors, such as polymorphisms in the genes implicated in the pathologic environment, pharmacodynamics, and metabolism of the disease or in the mechanism of action of the medications, influencing the effectiveness of these therapies. This review evaluates the impact of pharmacogenetics on the response to treatment with new therapies in patients diagnosed with MS. The results suggest that polymorphisms detected in the GSTP1, ITGA4, NQO1, AKT1, and GP6 genes, for treatment with natalizumab, ZMIZ1, for fingolimod and dimethyl fumarate, ADA, for cladribine, and NOX3, for dimethyl fumarate, may be used in the future as predictive markers of treatment response to new therapies in MS patients. However, there are few existing studies and their samples are small, making it difficult to generalize the role of these genes in treatment with new therapies. Studies with larger sample sizes and longer follow-up are therefore needed to confirm the results of these studies.

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