Binding of cholera toxin to pig intestinal mucosa glycosphingolipids: relationship with the ABO blood group system

Bennun, Fernando Ruben; Roth, German A.; Monferran, Clara G.; Cumar, Federico A.

doi:10.1128/iai.57.3.969-974.1989

Cited by 30 publications

(6 citation statements)

References 38 publications

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“…This probably depends on components, which are solely found in the intestine and especially in the mucus of pigs that allow the binding of the toxin and therefore impede its effects [ 53 ]. Moreover, these components, chemically identified as neutral glycosphingolipid, seem to depend on the ABO blood type of the infected organism [ 54 ]. Since 1977 [ 55 ] an association between blood type and severity of cholera infection was recognized.…”

Section: Discussionmentioning

confidence: 99%

Intestinal organoid-based 2D monolayers mimic physiological and pathophysiological properties of the pig intestine

Hoffmann¹,

Schnepel²,

Langeheine³

et al. 2021

PLoS ONE

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Gastrointestinal infectious diseases remain an important issue for human and animal health. Investigations on gastrointestinal infectious diseases are classically performed in laboratory animals leading to the problem that species-specific models are scarcely available, especially when it comes to farm animals. The 3R principles of Russel and Burch were achieved using intestinal organoids of porcine jejunum. These organoids seem to be a promising tool to generate species-specific in vitro models of intestinal epithelium. 3D Organoids were grown in an extracellular matrix and characterized by qPCR. Organoids were also seeded on permeable filter supports in order to generate 2D epithelial monolayers. The organoid-based 2D monolayers were characterized morphologically and were investigated regarding their potential to study physiological transport properties and pathophysiological processes. They showed a monolayer structure containing different cell types. Moreover, their functional activity was demonstrated by their increasing transepithelial electrical resistance over 18 days and by an active glucose transport and chloride secretion. Furthermore, the organoid-based 2D monolayers were also confronted with cholera toxin derived from Vibrio cholerae as a proof of concept. Incubation with cholera toxin led to an increase of short-circuit current indicating an enhanced epithelial chloride secretion, which is a typical characteristic of cholera infections. Taken this together, our model allows the investigation of physiological and pathophysiological mechanisms focusing on the small intestine of pigs. This is in line with the 3R principle and allows the reduction of classical animal experiments.

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Section: Discussionmentioning

confidence: 99%

Intestinal organoid-based 2D monolayers mimic physiological and pathophysiological properties of the pig intestine

Hoffmann¹,

Schnepel²,

Langeheine³

et al. 2021

PLoS ONE

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“…Some breeders have used this phenotype to breed disease resistant pigs. Moreover, cholera toxin and the heat labile toxin of E. coli bind to glycolipids in the intestinal mucosa of A pigs at higher levels than in non‐A pigs [32,33]. Similar effects have been seen in human infectious diseases.…”

Section: Ao Ss and H Systemsmentioning

confidence: 93%

Blood groups and transfusions in pigs

Smith

Newhouse

Naziruddin

et al. 2006

Xenotransplantation

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The blood groups of pigs are important to transplantation research because some are also important transplantation antigens and because pigs undergoing organ or hematopoietic transplantation may require transfusion support. There is considerable literature on the subject but much of it is not in transplant related journals. We will review this literature and also give some practical advice on transfusion support.

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“…The most active natural compound able to inhibit CT binding to membrane receptors is GM, (7). Chloroformmethanol-water (60:35:8, vol/vol/vol) extracts of A' and Amucin glycopeptides (1.5 mg) were examined for the presence of GM, by the method of Magnani et al 20as described previously (2). GM, was not detected in conditions in which 0.1 pmol of GM, standard was visualized.…”

Section: Methodsmentioning

confidence: 99%

Inhibition of cholera toxin binding to membrane receptors by pig gastric mucin-derived glycopeptides: differential effect depending on the ABO blood group antigenic determinants

1990

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The capacity of pig gastric mucin-derived glycopeptides to interfere with the binding of cholera toxin (CT) to membrane receptors was studied. Two types of glycopeptide preparations with or without human blood group A antigenic activity were assayed for comparison in a system in which the target for the toxin was rat erythrocyte ghosts. Blood group A-active glycopeptides (A+ glycopeptides) were more potent inhibitors for the toxin binding than those lacking group A activity (A- glycopeptides). The mean values of the 50% inhibitory dose revealed that the A+ glycopeptide preparations were 6.6-fold-more potent inhibitors than the A- ones (P less than 0.001). The inhibitory capacity of the different A+ glycopeptide preparations was not directly proportional to the group A antigenic titer. The A+ glycopeptides showed a higher capacity than the A- glycopeptides to interact with the toxin as revealed by CT-glycopeptide complex formation, which could be detected by Sephacryl S-400 chromatography. This result suggests that glycopeptide inhibition of CT binding to the erythrocyte ghosts is mediated by a competition between the GM1 receptors and the glycopeptides for the toxin. The differential effect between both types of glycoconjugates was independent of the way of measuring the amount of glycopeptides used (dry weight, carbohydrate or protein content). The existence in the gastrointestinal tract of mucins not carrying or carrying different ABO blood group determinants, which could behave as more or less potent inhibitors of CT binding to membrane receptors, may help to explain the relationship between ABO blood groups and severity of cholera.

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Binding of cholera toxin to pig intestinal mucosa glycosphingolipids: relationship with the ABO blood group system

Cited by 30 publications

References 38 publications

Intestinal organoid-based 2D monolayers mimic physiological and pathophysiological properties of the pig intestine

Intestinal organoid-based 2D monolayers mimic physiological and pathophysiological properties of the pig intestine

Blood groups and transfusions in pigs

Inhibition of cholera toxin binding to membrane receptors by pig gastric mucin-derived glycopeptides: differential effect depending on the ABO blood group antigenic determinants

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