Anthrax Lethal Toxin-induced gene expression changes in mouse lung

Eric K. Dumas, Philip M. Cox, Charles O Connor Fullenwider, Melissa Nguyen, Michael Centola, Mark Barton Frank, Igor Dozmorov, Judith A. James, A. Darise Farris

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

A major virulence factor of Bacillus anthracis is the anthrax Lethal Toxin (LeTx), a bipartite toxin composed of Protective Antigen and Lethal Factor. Systemic administration of LeTx to laboratory animals leads to death associated with vascular leakage and pulmonary edema. In this study, we investigated whether systemic exposure of mice to LeTx would induce gene expression changes associated with vascular/capillary leakage in lung tissue. We observed enhanced susceptibility of A/J mice to death by systemic LeTx administration compared to the C57BL/6 strain. LeTx-induced groups of both up- and down-regulated genes were observed in mouse lungs 6 h after systemic administration of wild type toxin compared to lungs of mice exposed to an inactive mutant form of the toxin. Lungs of the less susceptible C57BL/6 strain showed 80% fewer differentially expressed genes compared to lungs of the more sensitive A/J strain.Expression of genes known to regulate vascular permeability was modulated by LeTx in the lungs of the more susceptible A/J strain. Unexpectedly, the largest set of genes with altered expression was immune specific, characterized by the up-regulation of lymphoid genes and the down-regulation of myeloid genes. Transcripts encoding neutrophil chemoattractants, modulators of tumor regulation and angiogenesis were also differentially expressed in both mouse strains. These studies provide new directions for the investigation of vascular leakage and pulmonary edema induced by anthrax LeTx.

Original languageEnglish (US)
Pages (from-to)1111-1130
Number of pages20
JournalToxins
Volume3
Issue number9
DOIs
StatePublished - Sep 2011

Fingerprint

Gene expression
Genes
Gene Expression
Lung
Blood Vessels
Pulmonary Edema
Bacillus anthracis
Chemotactic Factors
Laboratory Animals
Capillary Permeability
Virulence Factors
Bacilli
Modulators
anthrax toxin
Tumors
Animals
Neutrophils
Up-Regulation
Down-Regulation
Tissue

Keywords

  • Gene expression
  • Lethal Toxin
  • Lung

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis

Cite this

Dumas, E. K., Cox, P. M., Fullenwider, C. O. C., Nguyen, M., Centola, M., Frank, M. B., ... Darise Farris, A. (2011). Anthrax Lethal Toxin-induced gene expression changes in mouse lung. Toxins, 3(9), 1111-1130. https://doi.org/10.3390/toxins3091111

Anthrax Lethal Toxin-induced gene expression changes in mouse lung. / Dumas, Eric K.; Cox, Philip M.; Fullenwider, Charles O Connor; Nguyen, Melissa; Centola, Michael; Frank, Mark Barton; Dozmorov, Igor; James, Judith A.; Darise Farris, A.

In: Toxins, Vol. 3, No. 9, 09.2011, p. 1111-1130.

Research output: Contribution to journalArticle

Dumas, EK, Cox, PM, Fullenwider, COC, Nguyen, M, Centola, M, Frank, MB, Dozmorov, I, James, JA & Darise Farris, A 2011, 'Anthrax Lethal Toxin-induced gene expression changes in mouse lung', Toxins, vol. 3, no. 9, pp. 1111-1130. https://doi.org/10.3390/toxins3091111
Dumas EK, Cox PM, Fullenwider COC, Nguyen M, Centola M, Frank MB et al. Anthrax Lethal Toxin-induced gene expression changes in mouse lung. Toxins. 2011 Sep;3(9):1111-1130. https://doi.org/10.3390/toxins3091111
Dumas, Eric K. ; Cox, Philip M. ; Fullenwider, Charles O Connor ; Nguyen, Melissa ; Centola, Michael ; Frank, Mark Barton ; Dozmorov, Igor ; James, Judith A. ; Darise Farris, A. / Anthrax Lethal Toxin-induced gene expression changes in mouse lung. In: Toxins. 2011 ; Vol. 3, No. 9. pp. 1111-1130.
@article{0ad46395297347b5b60421609436c3c3,
title = "Anthrax Lethal Toxin-induced gene expression changes in mouse lung",
abstract = "A major virulence factor of Bacillus anthracis is the anthrax Lethal Toxin (LeTx), a bipartite toxin composed of Protective Antigen and Lethal Factor. Systemic administration of LeTx to laboratory animals leads to death associated with vascular leakage and pulmonary edema. In this study, we investigated whether systemic exposure of mice to LeTx would induce gene expression changes associated with vascular/capillary leakage in lung tissue. We observed enhanced susceptibility of A/J mice to death by systemic LeTx administration compared to the C57BL/6 strain. LeTx-induced groups of both up- and down-regulated genes were observed in mouse lungs 6 h after systemic administration of wild type toxin compared to lungs of mice exposed to an inactive mutant form of the toxin. Lungs of the less susceptible C57BL/6 strain showed 80{\%} fewer differentially expressed genes compared to lungs of the more sensitive A/J strain.Expression of genes known to regulate vascular permeability was modulated by LeTx in the lungs of the more susceptible A/J strain. Unexpectedly, the largest set of genes with altered expression was immune specific, characterized by the up-regulation of lymphoid genes and the down-regulation of myeloid genes. Transcripts encoding neutrophil chemoattractants, modulators of tumor regulation and angiogenesis were also differentially expressed in both mouse strains. These studies provide new directions for the investigation of vascular leakage and pulmonary edema induced by anthrax LeTx.",
keywords = "Gene expression, Lethal Toxin, Lung",
author = "Dumas, {Eric K.} and Cox, {Philip M.} and Fullenwider, {Charles O Connor} and Melissa Nguyen and Michael Centola and Frank, {Mark Barton} and Igor Dozmorov and James, {Judith A.} and {Darise Farris}, A.",
year = "2011",
month = "9",
doi = "10.3390/toxins3091111",
language = "English (US)",
volume = "3",
pages = "1111--1130",
journal = "Toxins",
issn = "2072-6651",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "9",

}

TY - JOUR

T1 - Anthrax Lethal Toxin-induced gene expression changes in mouse lung

AU - Dumas, Eric K.

AU - Cox, Philip M.

AU - Fullenwider, Charles O Connor

AU - Nguyen, Melissa

AU - Centola, Michael

AU - Frank, Mark Barton

AU - Dozmorov, Igor

AU - James, Judith A.

AU - Darise Farris, A.

PY - 2011/9

Y1 - 2011/9

N2 - A major virulence factor of Bacillus anthracis is the anthrax Lethal Toxin (LeTx), a bipartite toxin composed of Protective Antigen and Lethal Factor. Systemic administration of LeTx to laboratory animals leads to death associated with vascular leakage and pulmonary edema. In this study, we investigated whether systemic exposure of mice to LeTx would induce gene expression changes associated with vascular/capillary leakage in lung tissue. We observed enhanced susceptibility of A/J mice to death by systemic LeTx administration compared to the C57BL/6 strain. LeTx-induced groups of both up- and down-regulated genes were observed in mouse lungs 6 h after systemic administration of wild type toxin compared to lungs of mice exposed to an inactive mutant form of the toxin. Lungs of the less susceptible C57BL/6 strain showed 80% fewer differentially expressed genes compared to lungs of the more sensitive A/J strain.Expression of genes known to regulate vascular permeability was modulated by LeTx in the lungs of the more susceptible A/J strain. Unexpectedly, the largest set of genes with altered expression was immune specific, characterized by the up-regulation of lymphoid genes and the down-regulation of myeloid genes. Transcripts encoding neutrophil chemoattractants, modulators of tumor regulation and angiogenesis were also differentially expressed in both mouse strains. These studies provide new directions for the investigation of vascular leakage and pulmonary edema induced by anthrax LeTx.

AB - A major virulence factor of Bacillus anthracis is the anthrax Lethal Toxin (LeTx), a bipartite toxin composed of Protective Antigen and Lethal Factor. Systemic administration of LeTx to laboratory animals leads to death associated with vascular leakage and pulmonary edema. In this study, we investigated whether systemic exposure of mice to LeTx would induce gene expression changes associated with vascular/capillary leakage in lung tissue. We observed enhanced susceptibility of A/J mice to death by systemic LeTx administration compared to the C57BL/6 strain. LeTx-induced groups of both up- and down-regulated genes were observed in mouse lungs 6 h after systemic administration of wild type toxin compared to lungs of mice exposed to an inactive mutant form of the toxin. Lungs of the less susceptible C57BL/6 strain showed 80% fewer differentially expressed genes compared to lungs of the more sensitive A/J strain.Expression of genes known to regulate vascular permeability was modulated by LeTx in the lungs of the more susceptible A/J strain. Unexpectedly, the largest set of genes with altered expression was immune specific, characterized by the up-regulation of lymphoid genes and the down-regulation of myeloid genes. Transcripts encoding neutrophil chemoattractants, modulators of tumor regulation and angiogenesis were also differentially expressed in both mouse strains. These studies provide new directions for the investigation of vascular leakage and pulmonary edema induced by anthrax LeTx.

KW - Gene expression

KW - Lethal Toxin

KW - Lung

UR - http://www.scopus.com/inward/record.url?scp=80053199327&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80053199327&partnerID=8YFLogxK

U2 - 10.3390/toxins3091111

DO - 10.3390/toxins3091111

M3 - Article

C2 - 22039574

AN - SCOPUS:80053199327

VL - 3

SP - 1111

EP - 1130

JO - Toxins

JF - Toxins

SN - 2072-6651

IS - 9

ER -