Effects by anthrax toxins on hematopoiesis

A key role for cytokines as mediators

Pranela Rameshwar, Elaine W. Wong, Nancy Connell

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

An understanding of anthrax toxins on the emerging immune system and blood production are significant to medicine. This study examined the effects of anthrax toxin on hematopoiesis and determined roles for cytokines. Anthrax holotoxin toxin is three components: protective antigen (PA) binds to the target cell and mediates the entry of lethal factor (LF) and edema factor (EF). Anthrax toxin dramatically inhibits signaling in immune cells. We first identified the cell subsets that interacted with the protective antigen (PA) and then studied the effects on hematopoietic progenitors in clonogenic assays: granulocytic-monocytic (CFU-GM) and late erythroid (CFU-E). Multi-color immunofluorescence with FITC-PA indicated its interaction with early and late myeloid cells. Clonogenic assays, in the presence or absence of holotoxin and individual toxin proteins resulted in significant suppression by hologenic toxic alone, despite the presence of growth-promoting cytokines. Antibodies to anthrax receptor (ATR1) reversed the suppressive effects, indicating specificity. Monomeric proteins showed different effects on myeloid and erythroid progenitors. Suppression was not due to cell death, based on undetectable active caspase 3. Cytokine array analyses with supernatants from toxin-stimulated stroma showed an increase in the hematopoietic suppressor, MIP-1α. This finding, in addition to our previous studies, showing an increase in IL-10, suggested indirect roles for cytokines in toxin-mediated hematopoietic suppression. The chemokine, SDF-1α was increased. Since SDF-1 is involved in the mobilization of hematopoietic cells, it is likely that anthrax holotoxin could induce cell exit from BM. In summary, anthrax holotoxin, but not individual toxins, exerted hematopoietic effects on myeloid and erythroid progenitors via specific receptor, partly through the induction of cytokines.

Original languageEnglish (US)
Pages (from-to)143-149
Number of pages7
JournalCytokine
Volume57
Issue number1
DOIs
StatePublished - Jan 1 2012

Fingerprint

Hematopoiesis
Anthrax
Cytokines
Antigens
Assays
Granulocyte-Macrophage Progenitor Cells
Fluorescein-5-isothiocyanate
Immune system
Poisons
Cell death
Myeloid Cells
Chemokines
Caspase 3
Interleukin-10
Medicine
Fluorescent Antibody Technique
Immune System
Proteins
Blood
Cell Death

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Hematology
  • Biochemistry
  • Immunology and Allergy
  • Immunology

Cite this

Rameshwar, Pranela ; Wong, Elaine W. ; Connell, Nancy. / Effects by anthrax toxins on hematopoiesis : A key role for cytokines as mediators. In: Cytokine. 2012 ; Vol. 57, No. 1. pp. 143-149.
@article{a12f7a7fa19941b6abf3f06fe66533e3,
title = "Effects by anthrax toxins on hematopoiesis: A key role for cytokines as mediators",
abstract = "An understanding of anthrax toxins on the emerging immune system and blood production are significant to medicine. This study examined the effects of anthrax toxin on hematopoiesis and determined roles for cytokines. Anthrax holotoxin toxin is three components: protective antigen (PA) binds to the target cell and mediates the entry of lethal factor (LF) and edema factor (EF). Anthrax toxin dramatically inhibits signaling in immune cells. We first identified the cell subsets that interacted with the protective antigen (PA) and then studied the effects on hematopoietic progenitors in clonogenic assays: granulocytic-monocytic (CFU-GM) and late erythroid (CFU-E). Multi-color immunofluorescence with FITC-PA indicated its interaction with early and late myeloid cells. Clonogenic assays, in the presence or absence of holotoxin and individual toxin proteins resulted in significant suppression by hologenic toxic alone, despite the presence of growth-promoting cytokines. Antibodies to anthrax receptor (ATR1) reversed the suppressive effects, indicating specificity. Monomeric proteins showed different effects on myeloid and erythroid progenitors. Suppression was not due to cell death, based on undetectable active caspase 3. Cytokine array analyses with supernatants from toxin-stimulated stroma showed an increase in the hematopoietic suppressor, MIP-1α. This finding, in addition to our previous studies, showing an increase in IL-10, suggested indirect roles for cytokines in toxin-mediated hematopoietic suppression. The chemokine, SDF-1α was increased. Since SDF-1 is involved in the mobilization of hematopoietic cells, it is likely that anthrax holotoxin could induce cell exit from BM. In summary, anthrax holotoxin, but not individual toxins, exerted hematopoietic effects on myeloid and erythroid progenitors via specific receptor, partly through the induction of cytokines.",
author = "Pranela Rameshwar and Wong, {Elaine W.} and Nancy Connell",
year = "2012",
month = "1",
day = "1",
doi = "https://doi.org/10.1016/j.cyto.2011.10.013",
language = "English (US)",
volume = "57",
pages = "143--149",
journal = "Cytokine",
issn = "1043-4666",
publisher = "Academic Press Inc.",
number = "1",

}

Effects by anthrax toxins on hematopoiesis : A key role for cytokines as mediators. / Rameshwar, Pranela; Wong, Elaine W.; Connell, Nancy.

In: Cytokine, Vol. 57, No. 1, 01.01.2012, p. 143-149.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Effects by anthrax toxins on hematopoiesis

T2 - A key role for cytokines as mediators

AU - Rameshwar, Pranela

AU - Wong, Elaine W.

AU - Connell, Nancy

PY - 2012/1/1

Y1 - 2012/1/1

N2 - An understanding of anthrax toxins on the emerging immune system and blood production are significant to medicine. This study examined the effects of anthrax toxin on hematopoiesis and determined roles for cytokines. Anthrax holotoxin toxin is three components: protective antigen (PA) binds to the target cell and mediates the entry of lethal factor (LF) and edema factor (EF). Anthrax toxin dramatically inhibits signaling in immune cells. We first identified the cell subsets that interacted with the protective antigen (PA) and then studied the effects on hematopoietic progenitors in clonogenic assays: granulocytic-monocytic (CFU-GM) and late erythroid (CFU-E). Multi-color immunofluorescence with FITC-PA indicated its interaction with early and late myeloid cells. Clonogenic assays, in the presence or absence of holotoxin and individual toxin proteins resulted in significant suppression by hologenic toxic alone, despite the presence of growth-promoting cytokines. Antibodies to anthrax receptor (ATR1) reversed the suppressive effects, indicating specificity. Monomeric proteins showed different effects on myeloid and erythroid progenitors. Suppression was not due to cell death, based on undetectable active caspase 3. Cytokine array analyses with supernatants from toxin-stimulated stroma showed an increase in the hematopoietic suppressor, MIP-1α. This finding, in addition to our previous studies, showing an increase in IL-10, suggested indirect roles for cytokines in toxin-mediated hematopoietic suppression. The chemokine, SDF-1α was increased. Since SDF-1 is involved in the mobilization of hematopoietic cells, it is likely that anthrax holotoxin could induce cell exit from BM. In summary, anthrax holotoxin, but not individual toxins, exerted hematopoietic effects on myeloid and erythroid progenitors via specific receptor, partly through the induction of cytokines.

AB - An understanding of anthrax toxins on the emerging immune system and blood production are significant to medicine. This study examined the effects of anthrax toxin on hematopoiesis and determined roles for cytokines. Anthrax holotoxin toxin is three components: protective antigen (PA) binds to the target cell and mediates the entry of lethal factor (LF) and edema factor (EF). Anthrax toxin dramatically inhibits signaling in immune cells. We first identified the cell subsets that interacted with the protective antigen (PA) and then studied the effects on hematopoietic progenitors in clonogenic assays: granulocytic-monocytic (CFU-GM) and late erythroid (CFU-E). Multi-color immunofluorescence with FITC-PA indicated its interaction with early and late myeloid cells. Clonogenic assays, in the presence or absence of holotoxin and individual toxin proteins resulted in significant suppression by hologenic toxic alone, despite the presence of growth-promoting cytokines. Antibodies to anthrax receptor (ATR1) reversed the suppressive effects, indicating specificity. Monomeric proteins showed different effects on myeloid and erythroid progenitors. Suppression was not due to cell death, based on undetectable active caspase 3. Cytokine array analyses with supernatants from toxin-stimulated stroma showed an increase in the hematopoietic suppressor, MIP-1α. This finding, in addition to our previous studies, showing an increase in IL-10, suggested indirect roles for cytokines in toxin-mediated hematopoietic suppression. The chemokine, SDF-1α was increased. Since SDF-1 is involved in the mobilization of hematopoietic cells, it is likely that anthrax holotoxin could induce cell exit from BM. In summary, anthrax holotoxin, but not individual toxins, exerted hematopoietic effects on myeloid and erythroid progenitors via specific receptor, partly through the induction of cytokines.

UR - http://www.scopus.com/inward/record.url?scp=84155167483&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84155167483&partnerID=8YFLogxK

U2 - https://doi.org/10.1016/j.cyto.2011.10.013

DO - https://doi.org/10.1016/j.cyto.2011.10.013

M3 - Article

VL - 57

SP - 143

EP - 149

JO - Cytokine

JF - Cytokine

SN - 1043-4666

IS - 1

ER -