Erythrocytic mobilization enhanced by the granulocyte colony-stimulating factor is associated with reduced anthrax-lethal-toxin-induced mortality in mice

Hsin-Hou Chang; Ya-Wen Chiang; Ting-Kai Lin; Guan-Ling Lin; You-Yen Lin; Jyh-Hwa Kau; Hsin-Hsien Huang; Hui-Ling Hsu; Jen-Hung Wang; Der-Shan Sun

doi:10.1371/journal.pone.0111149

Erythrocytic mobilization enhanced by the granulocyte colony-stimulating factor is associated with reduced anthrax-lethal-toxin-induced mortality in mice

PLoS One. 2014 Nov 10;9(11):e111149. doi: 10.1371/journal.pone.0111149. eCollection 2014.

Authors

Affiliations

¹ Department of Molecular Biology and Human Genetics, Tzu-Chi University, Hualien, Taiwan; Institute of Medical Sciences, Tzu-Chi University, Hualien, Taiwan.
² Department of Molecular Biology and Human Genetics, Tzu-Chi University, Hualien, Taiwan.
³ Institute of Medical Sciences, Tzu-Chi University, Hualien, Taiwan.
⁴ Department of Microbiology and Immunology, National Defense Medical Center, Taipei, Taiwan.
⁵ Institute of Preventive Medicine, National Defense Medical Center, Taipei, Taiwan.
⁶ Department of Medical Research, Tzu Chi General Hospital, Hualien, Taiwan.

Abstract

Anthrax lethal toxin (LT), one of the primary virulence factors of Bacillus anthracis, causes anthrax-like symptoms and death in animals. Experiments have indicated that levels of erythrocytopenia and hypoxic stress are associated with disease severity after administering LT. In this study, the granulocyte colony-stimulating factor (G-CSF) was used as a therapeutic agent to ameliorate anthrax-LT- and spore-induced mortality in C57BL/6J mice. We demonstrated that G-CSF promoted the mobilization of mature erythrocytes to peripheral blood, resulting in a significantly faster recovery from erythrocytopenia. In addition, combined treatment using G-CSF and erythropoietin tended to ameliorate B. anthracis-spore-elicited mortality in mice. Although specific treatments against LT-mediated pathogenesis remain elusive, these results may be useful in developing feasible strategies to treat anthrax.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Analysis of Variance
Animals
Antigens, Bacterial / poisoning
Antigens, Bacterial / toxicity*
Bacterial Toxins / poisoning
Bacterial Toxins / toxicity*
Erythrocytes / drug effects*
Erythrocytes / physiology
Erythroid Precursor Cells
Erythropoiesis / drug effects
Erythropoiesis / physiology
Erythropoietin / pharmacology*
Flow Cytometry
Granulocyte Colony-Stimulating Factor / pharmacology*
Granulocyte Colony-Stimulating Factor / therapeutic use
Kaplan-Meier Estimate
Mice
Mice, Inbred C57BL

Substances

Antigens, Bacterial
Bacterial Toxins
anthrax toxin
Erythropoietin
Granulocyte Colony-Stimulating Factor

Grants and funding

This work was supported by grants of National Science Council http://web1.nsc.gov.tw/mp.aspx (NSC 96-2311-B-320-005-MY3 and NSC 99-2311-B-320-003-MY3) and Tzu-Chi University http://www.tcu.edu.tw/ (610400130). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.