Back to Search Start Over

Suppressive effects of anthrax lethal toxin on megakaryopoiesis

Authors :
Der-Shan Sun
Tsung-Pao Wang
Po-Kong Chen
Yi-Ling Lai
Ming-Chun Hsieh
Hui-Ling Hsu
Hsin-Hou Chang
Guan-Ling Lin
Jyh-Hwa Kau
Ting-Kai Lin
Chi-Yuan Liao
Hsin-Hsien Huang
Source :
PLoS ONE, Vol 8, Iss 3, p e59512 (2013), PLoS ONE
Publication Year :
2013
Publisher :
Public Library of Science (PLoS), 2013.

Abstract

Anthrax lethal toxin (LT) is a major virulence factor of Bacillus anthracis. LT challenge suppresses platelet counts and platelet function in mice, however, the mechanism responsible for thrombocytopenia remains unclear. LT inhibits cellular mitogen-activated protein kinases (MAPKs), which are vital pathways responsible for cell survival, differentiation, and maturation. One of the MAPKs, the MEK1/2-extracellular signal-regulated kinase pathway, is particularly important in megakaryopoiesis. This study evaluates the hypothesis that LT may suppress the progenitor cells of platelets, thereby inducing thrombocytopenic responses. Using cord blood-derived CD34(+) cells and mouse bone marrow mononuclear cells to perform in vitro differentiation, this work shows that LT suppresses megakaryopoiesis by reducing the survival of megakaryocytes. Thrombopoietin treatments can reduce thrombocytopenia, megakaryocytic suppression, and the quick onset of lethality in LT-challenged mice. These results suggest that megakaryocytic suppression is one of the mechanisms by which LT induces thrombocytopenia. These findings may provide new insights for developing feasible approaches against anthrax.

Details

Language :
English
ISSN :
19326203
Volume :
8
Issue :
3
Database :
OpenAIRE
Journal :
PLoS ONE
Accession number :
edsair.doi.dedup.....cac7b601c488270114a09c2050f117dc