Toxicity of Anthrax Toxin Is Influenced by Receptor Expression

Taft, Sarah C.; Weiss, Alison A.

doi:10.1128/cvi.00103-08

Cited by 9 publications

(11 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Indeed, contradictory results of this relationship between anthrax receptor expression level and cytotoxic effects have previously been reported in the literature, in various cell types. For example, Taft and Weiss (2005) showed that anthrax toxin toxicity was influenced by ANTXR expression, while other studies showed that despite detection of ANTXR1 and ANTXR2 mRNA levels, cells were resistant to the effects of LeTx (Abi-Habib et al 2005;Wu et al 2009). Presently, we are unable to explain the relationship between the toxin receptor expression levels and lethal toxin cytotoxicity in lung cells.…”

Section: Discussionmentioning

confidence: 99%

“…; Bonuccelli et al . ; Taft and Weiss ). However, the exact cellular distribution of ANTXR1 and ANTXR2 in human lung tissue has not been reported to date.…”

Section: Introductionmentioning

confidence: 99%

“…These two receptors share 40% of their amino acid sequence overall, but share 60% in the von Willebrand factor A-like region, where PA binding occurs (Young and Collier 2007). A series of studies have demonstrated that anthrax infection is correlated with high expression levels of the anthrax toxin receptors (Banks et al 2005;Bonuccelli et al 2005;Taft and Weiss 2005). However, the exact cellular distribution of ANT-XR1 and ANTXR2 in human lung tissue has not been reported to date.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Bacillus anthracis lethal toxin induces cell-type-specific cytotoxicity in human lung cell lines

et al. 2014

View full text Add to dashboard Cite

Aims: Inhalational anthrax is caused by the entry of Bacillus anthracis spores into the lung. Inhaled spores are phagocytosed by alveolar macrophages. Bacilli then escape from the macrophage and spread to other cells, initiating a systemic anthrax infection. Based on the pathological studies of primate and human inhalational anthrax cases, it appears that lung tissue injury is a lethal consequence of the disease. Although the cytotoxicity of anthrax lethal toxin to macrophages is well known, it is not clear how anthrax toxin affects the various lung cell types. Methods and Results: Using model cell lines representing different physiological compartments of the lung, we have investigated the cytotoxic effects of anthrax lethal toxin. The cell response was evaluated through MTT metabolism, neutral red uptake, initiation of apoptosis, and expression and binding activity of anthrax toxin receptors. We found that a human small airway epithelial cell line, HSAEC, was susceptible to anthrax lethal toxin. The other cell lines, A549, MRC-5, H358 and SKLU-1, displayed resistance to anthrax lethal toxin-mediated toxicity, although the expression of anthrax toxin receptors was detected in all the cell lines tested. Conclusions: Our results indicate that cell-type-specific toxicity may be induced by anthrax lethal toxin in human lung tissues and does not correlate with anthrax toxin receptor expression levels. Significance and Impact of the Study: This work suggests that cell-type-specific cytotoxicity of anthrax toxin in lung cells may cause subsequent lung disease progression. It may explain the initial pathogenic step of inhalational anthrax.

show abstract

Section: Discussionmentioning

confidence: 99%

“…; Bonuccelli et al . ; Taft and Weiss ). However, the exact cellular distribution of ANTXR1 and ANTXR2 in human lung tissue has not been reported to date.…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Bacillus anthracis lethal toxin induces cell-type-specific cytotoxicity in human lung cell lines

et al. 2014

View full text Add to dashboard Cite

show abstract

“…The mere binding of TEM8 or preventing TEM8 from binding its physiologic partner may be enough to decrease tumor vessel density. For strategies using anthrax toxin components, the outcome may be explained by protective antigen forming a pore in cell membranes that disrupts metabolic activity and causes cell swelling (29). In the case of therapeutic molecules that either bind TEM8 or block interaction with a physiologic partner, their effect may be explained Fig.…”

Section: Discussionmentioning

confidence: 99%

Targeting Tumor Endothelial Marker 8 in the Tumor Vasculature of Colorectal Carcinomas in Mice

Fernando

Fletcher²

2009

Cancer Research

View full text Add to dashboard Cite

Tumor endothelial marker 8 (TEM8) is a recently described protein that is preferentially expressed within tumor endothelium. We have developed a fusion protein that targets TEM8 and disrupts tumor vasculature by promoting localized thrombosis. Fusion protein specificity and function were evaluated using Western blot analysis, ELISA, and enzymatic assays. A xenograft model of colorectal carcinoma was used to test the efficacy of targeted and control fusion proteins. Mice treated with the gene encoding anti-TEM8/truncated tissue factor exhibited a 53% reduction in tumor volume when compared with the untreated animals (P < 0.0001; n = 10) and achieved a 49% increase in tumor growth delay by Kaplan-Meier analysis (P = 0.0367; n = 6). Immunohistochemistry confirmed tumor endothelial expression of TEM8, fusion protein homing to tumor vasculature, decrease in vessel density, and localized areas of thrombosis. These data support the hypothesis that targeting TEM8 can be an effective approach to influence tumor development by disrupting tumor vasculature. [Cancer Res 2009;69(12):5126-32]

show abstract

“…Oral consumption of spores can lead to an oropharyngeal or gastrointestinal infection, which can be fatal. In contrast, respiratory exposure to spores leads directly to a fulminant systemic disease which is fatal without treatment (4,5). In respiratory anthrax in humans, the incubation time from infection until the onset of symptoms is estimated to be 1 to 7 days.…”

mentioning

confidence: 99%

Efficacy of Single and Combined Antibiotic Treatments of Anthrax in Rabbits

Weiss

Altboum

Glinert

et al. 2015

Antimicrob Agents Chemother

View full text Add to dashboard Cite

Respiratory anthrax is a fatal disease in the absence of early treatment with antibiotics. Rabbits are highly susceptible to infection with Bacillus anthracis spores by intranasal instillation, succumbing within 2 to 4 days postinfection. This study aims to test the efficiency of antibiotic therapy to treat systemic anthrax in this relevant animal model. Delaying the initiation of antibiotic administration to more than 24 h postinfection resulted in animals with systemic anthrax in various degrees of bacteremia and toxemia. As the onset of symptoms in humans was reported to start on days 1 to 7 postexposure, delaying the initiation of treatment by 24 to 48 h (time frame for mass distribution of antibiotics) may result in sick populations. We evaluated the efficacy of antibiotic administration as a function of bacteremia levels at the time of treatment initiation. Here we compare the efficacy of treatment with clarithromycin, amoxicillin-clavulanic acid (Augmentin), imipenem, vancomycin, rifampin, and linezolid to the previously reported efficacy of doxycycline and ciprofloxacin. We demonstrate that treatment with amoxicillin-clavulanic acid, imipenem, vancomycin, and linezolid were as effective as doxycycline and ciprofloxacin, curing rabbits exhibiting bacteremia levels of up to 10 5 CFU/ml. Clarithromycin and rifampin were shown to be effective only as a postexposure prophylactic treatment but failed to treat the systemic (bacteremic) phase of anthrax. Furthermore, we evaluate the contribution of combined treatment of clindamycin and ciprofloxacin, which demonstrated improvement in efficacy compared to ciprofloxacin alone.

show abstract

Toxicity of Anthrax Toxin Is Influenced by Receptor Expression

Cited by 9 publications

References 44 publications

Bacillus anthracis lethal toxin induces cell-type-specific cytotoxicity in human lung cell lines

Bacillus anthracis lethal toxin induces cell-type-specific cytotoxicity in human lung cell lines

Targeting Tumor Endothelial Marker 8 in the Tumor Vasculature of Colorectal Carcinomas in Mice

Efficacy of Single and Combined Antibiotic Treatments of Anthrax in Rabbits

Contact Info

Product

Resources

About