scholarly journals Clostridium perfringens β-toxin binding to vascular endothelial cells in a human case of enteritis necroticans

2009 ◽  
Vol 58 (6) ◽  
pp. 826-828 ◽  
Author(s):  
Julien Miclard ◽  
Joop van Baarlen ◽  
Marianne Wyder ◽  
Benno Grabscheid ◽  
Horst Posthaus
Keyword(s):  
Endothelial Cells ◽  
Clostridium Perfringens ◽  
Vascular Endothelial Cells ◽  
Direct Interaction ◽  
Human Case ◽  
Small Intestinal Mucosa ◽  
Toxin Binding ◽  
Intestinal Lesions ◽  
Small Intestinal ◽  
Enteritis Necroticans

Clostridium perfringens type C-induced enteritis necroticans is a rare but often fatal disease in humans. A consistent histopathological finding is an acute, deep necrosis of the small intestinal mucosa associated with acute vascular necrosis and massive haemorrhage in the lamina propria and submucosa. Retrospective immunohistochemical investigations of tissues from a diabetic adult who died of enteritis necroticans revealed endothelial localization of C. perfringens β-toxin in small intestinal lesions. Our results indicate that vascular necrosis might be induced by a direct interaction between C. perfringens β-toxin and endothelial cells and that targeted disruption of endothelial cells plays a role in the pathogenesis of enteritis necroticans.

scholarly journals Synergistic Effects of Clostridium perfringens Enterotoxin and Beta Toxin in Rabbit Small Intestinal Loops

2014 ◽  
Vol 82 (7) ◽  
pp. 2958-2970 ◽  
Author(s):  
Menglin Ma ◽  
Abhijit Gurjar ◽  
James R. Theoret ◽  
Jorge P. Garcia ◽  
Juliann Beingesser ◽  
...  
Keyword(s):  
Clostridium Perfringens ◽  
Synergistic Effects ◽  
Fluid Accumulation ◽  
Content Type ◽  
Positive Type ◽  
Intestinal Infections ◽  
Type C ◽  
Small Intestinal ◽  
Beta Toxin ◽  
Enteritis Necroticans

ABSTRACTThe ability ofClostridium perfringenstype C to cause human enteritis necroticans (EN) is attributed to beta toxin (CPB). However, many EN strains also expressC. perfringensenterotoxin (CPE), suggesting that CPE could be another contributor to EN. Supporting this possibility, lysate supernatants from modified Duncan-Strong sporulation (MDS) medium cultures of three CPE-positive type C EN strains caused enteropathogenic effects in rabbit small intestinal loops, which is significant since CPE is produced only during sporulation and sinceC. perfringenscan sporulate in the intestines. Consequently, CPE and CPB contributions to the enteropathogenic effects of MDS lysate supernatants of CPE-positive type C EN strain CN3758 were evaluated using isogeniccpbandcpenull mutants. While supernatants of wild-type CN3758 MDS lysates induced significant hemorrhagic lesions and luminal fluid accumulation, MDS lysate supernatants of thecpbandcpemutants caused neither significant damage nor fluid accumulation. This attenuation was attributable to inactivating these toxin genes since complementing thecpemutant or reversing thecpbmutation restored the enteropathogenic effects of MDS lysate supernatants. Confirming that both CPB and CPE are needed for the enteropathogenic effects of CN3758 MDS lysate supernatants, purified CPB and CPE at the same concentrations found in CN3758 MDS lysates also acted together synergistically in rabbit small intestinal loops; however, only higher doses of either purified toxin independently caused enteropathogenic effects. These findings provide the first evidence for potential synergistic toxin interactions duringC. perfringensintestinal infections and support a possible role for CPE, as well as CPB, in some EN cases.

scholarly journals Clostridium perfringens Epsilon-Toxin Increases Permeability of Single Perfused Microvessels of Rat Mesentery

2005 ◽  
Vol 73 (8) ◽  
pp. 4879-4887 ◽  
Author(s):  
R. H. Adamson ◽  
J. C. Ly ◽  
M. Fernandez-Miyakawa ◽  
S. Ochi ◽  
J. Sakurai ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Clostridium Perfringens ◽  
Vascular Endothelial Cells ◽  
Intestinal Barrier ◽  
Endothelial Damage ◽  
Direct Access ◽  
Dependent Manner ◽  
Vascular Endothelial ◽  
Rat Mesentery ◽  
Epsilon Toxin

ABSTRACT Epsilon-toxin, the primary virulence factor of Clostridium perfringens type D, causes mortality in livestock, particularly sheep and goats, in which it induces an often-fatal enterotoxemia. It is believed to compromise the intestinal barrier and then enter the gut vasculature, from which it is carried systemically, causing widespread vascular endothelial damage and edema. Here we used single perfused venular microvessels in rat mesentery, which enabled direct observation of permeability properties of the in situ vascular wall during exposure to toxin. We determined the hydraulic conductivity (Lp ) of microvessels as a measure of the response to epsilon-toxin. We found that microvessels were highly sensitive to toxin. At 10 μg ml−1 the Lp increased irreversibly to more than 15 times the control value by 10 min. At 0.3 μg ml−1 no increase in Lp was observed for up to 90 min. The toxin-induced increase in Lp was consistent with changes in ultrastructure of microvessels exposed to the toxin. Those microvessels exhibited gaps either between or through endothelial cells where perfusate had direct access to the basement membrane. Many endothelial cells appeared necrotic, highly attenuated, and with dense cytoplasm. We showed that epsilon-toxin, in a time- and dose-dependent manner, rapidly and irreversibly compromised the barrier function of venular microvessel endothelium. The results conformed to the hypothesis that epsilon-toxin interacts with vascular endothelial cells and increases the vessel wall permeability by direct damage of the endothelium.

Enhancement of endothelial cAMP accumulation by adenine nucleotides: role of methylxanthine-sensitive sites

1993 ◽  
Vol 264 (5) ◽  
pp. H1498-H1503 ◽  
Author(s):  
S. Cote ◽  
J. Van Sande ◽  
J. M. Boeynaems
Keyword(s):  
Endothelial Cells ◽  
Inositol Phosphates ◽  
Vascular Endothelial Cells ◽  
Adenine Nucleotides ◽  
Direct Interaction ◽  
P2 Receptors ◽  
Camp Content ◽  
Aortic Endothelial Cells ◽  
Nitric Oxide Release ◽  
Kinase C

ATP is a well-known inducer of prostacyclin and nitric oxide release from vascular endothelial cells. These responses are mediated by P2 receptors coupled to a phospholipase C. We have investigated the influence of ATP on the control of adenosine 3',5'-cyclic monophosphate (cAMP) in bovine aortic endothelial cells. ATP produced a slight increase in the cAMP content of unstimulated endothelial cells. A more impressive response to ATP (5-fold) was observed in forskolin-stimulated cells. The rank orders of potency of various ATP analogues were strikingly different for the increase in cAMP and the accumulation of inositol phosphates. The action of ATP was unaffected by indomethacin. Protein kinase C downregulation produced only a partial inhibition of the ATP response. The effect of phorbol 12-myristate 13-acetate and bradykinin on the forskolin-induced accumulation of cAMP was much smaller than that of ATP. Neither adenosine deaminase nor AMP deaminase decreased the response to ATP, which thus cannot result from the ATP degradation into adenosine. However, 8-(p-sulfophenyl)theophylline inhibited the responses to both ATP and adenosine. In conclusion, ATP enhances the accumulation of cAMP in endothelial cells. This action appears to be the sum of two components: a minor one resulting from kinase C activation and a major one mediated either by a direct interaction of ATP with A2 receptors, or by putative methylxanthine-sensitive P2 receptors.

Effect OF Clostridium perfringens Beta Toxin on the Porcine Small Intestinal Mucosa

2015 ◽  
Vol 152 (1) ◽  
pp. 56
Author(s):  
S. Roos ◽  
M. Wyder ◽  
N. Regenscheit ◽  
A. Candi ◽  
C. Nathues ◽  
...  
Keyword(s):  
Clostridium Perfringens ◽  
Intestinal Mucosa ◽  
Small Intestinal Mucosa ◽  
Small Intestinal ◽  
Beta Toxin

scholarly journals miR-29b represses intestinal mucosal growth by inhibiting translation of cyclin-dependent kinase 2

2013 ◽  
Vol 24 (19) ◽  
pp. 3038-3046 ◽  
Author(s):  
Lan Xiao ◽  
Jaladanki N. Rao ◽  
Tongtong Zou ◽  
Lan Liu ◽  
Shan Cao ◽  
...  
Keyword(s):  
Intestinal Mucosa ◽  
Direct Interaction ◽  
The Body ◽  
Locked Nucleic Acid ◽  
Small Intestinal Mucosa ◽  
Cyclin Dependent Kinase ◽  
Systemic Delivery ◽  
Small Intestinal ◽  
Mucosal Growth ◽  
Cdk2 Expression

The epithelium of the intestinal mucosa is a rapidly self-renewing tissue in the body, and defects in the renewal process occur commonly in various disorders. microRNAs (miRNAs) posttranscriptionally regulate gene expression and are implicated in many aspects of cellular physiology. Here we investigate the role of miRNA-29b (miR-29b) in the regulation of normal intestinal mucosal growth and further validate its target mRNAs. miRNA expression profiling studies reveal that growth inhibition of the small intestinal mucosa is associated with increased expression of numerous miRNAs, including miR-29b. The simple systemic delivery of locked nucleic acid–modified, anti–miR-29b-reduced endogenous miR-29b levels in the small intestinal mucosa increases cyclin-dependent kinase 2 (CDK2) expression and stimulates mucosal growth. In contrast, overexpression of the miR-29b precursor in intestinal epithelial cells represses CDK2 expression and results in growth arrest in G1 phase. miR-29b represses CDK2 translation through direct interaction with the cdk2 mRNA via its 3′-untranslated region (3′-UTR), whereas point mutation of miR-29b binding site in the cdk2 3′-UTR prevents miR-29b–induced repression of CDK2 translation. These results indicate that miR-29b inhibits intestinal mucosal growth by repressing CDK2 translation.

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