Erythropoiesis suppression is associated with anthrax lethal toxin-mediated pathogenic progression
| Autor: | Tsung-Pao Wang, Der-Shan Sun, Jyh-Hwa Kau, Hsin-Hsien Huang, Hsin-Hou Chang, Chih-Yu Chiang, Wen-Bin Lin, Ting-Kai Lin, Chih-Hsien Liao, Chi-Yuan Liao, Ya-Wen Chiang, Yo-Yin Lin, Po-Kong Chen, Hui-Ling Hsu |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Male
Bacterial Diseases Mouse Red Cells lcsh:Medicine Apoptosis Signal transduction Virulence factor Pathogenesis Mice Molecular cell biology Erythropoiesis lcsh:Science Multidisciplinary biology Kinase Signaling cascades Anemia Cell Differentiation Animal Models Hematology Bacillus anthracis Infectious Diseases medicine.anatomical_structure Disease Progression Medicine Research Article medicine.drug MAPK signaling cascades Bacterial Toxins Hemolysis Anthrax Colony-Forming Units Assay Model Organisms Erythroid Cells medicine Animals Humans Erythropoietin Biology Antigens Bacterial lcsh:R medicine.disease biology.organism_classification Survival Analysis Hematopoiesis Mice Inbred C57BL Proteolysis Immunology Biocatalysis lcsh:Q Bone marrow Developmental Biology |
| Zdroj: | PLoS ONE, Vol 8, Iss 8, p e71718 (2013) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | Anthrax is a disease caused by the bacterium Bacillus anthracis, which results in high mortality in animals and humans. Although some of the mechanisms are already known such as asphyxia, extensive knowledge of molecular pathogenesis of this disease is deficient and remains to be further investigated. Lethal toxin (LT) is a major virulence factor of B. anthracis and a specific inhibitor/protease of mitogen-activated protein kinase kinases (MAPKKs). Anthrax LT causes lethality and induces certain anthrax-like symptoms, such as anemia and hypoxia, in experimental mice. Mitogen-activated protein kinases (MAPKs) are the downstream pathways of MAPKKs, and are important for erythropoiesis. This prompted us to hypothesize that anemia and hypoxia may in part be exacerbated by erythropoietic dysfunction. As revealed by colony-forming cell assays in this study, LT challenges significantly reduced mouse erythroid progenitor cells. In addition, in a proteolytic activity-dependent manner, LT suppressed cell survival and differentiation of cord blood CD34(+)-derived erythroblasts in vitro. Suppression of cell numbers and the percentage of erythroblasts in the bone marrow were detected in LT-challenged C57BL/6J mice. In contrast, erythropoiesis was provoked through treatments of erythropoietin, significantly ameliorating the anemia and reducing the mortality of LT-treated mice. These data suggested that suppressed erythropoiesis is part of the pathophysiology of LT-mediated intoxication. Because specific treatments to overcome LT-mediated pathogenesis are still lacking, these efforts may help the development of effective treatments against anthrax. |
| Databáze: | OpenAIRE |
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