Concurrent partial body radiation prevents cytokine mobilization of blood progenitor cells: An effect mediated by a circulating factor

John G Sharp, A. Kessinger, S. R. Clausen, S. L. Mann, B. O'Kane-Murphy

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Mobilization of stem and progenitor cells into blood, which facilitates the collection of blood-derived autograft and allograft products, can be accomplished with administration of myelosuppressive chemotherapy, hematopoietic growth factors, or both. Autologous donor indifference to mobilization attempts has been correlated with prior administration of chemotherapy and radiation therapy. To investigate whether concurrent administration of radiation therapy inhibits mobilization, five daily injections of a potent combination of mobilizing cytokines, 500 U/kg erythropoietin (EPO) plus 15 μg/kg G-CSF, were administered each morning to Balb/c mice. Each afternoon, a 2 Gy fraction of Co-60 radiation was administered to either the lower limb or the upper or lower hemibody. Each day, mice were necropsied, and blood stem cell mobilization was determined by assaying the number of hematopoietic colony-forming cells in the blood and in the spleen. Unirradiated cytokine-injected mice showed a significant mobilization effect evident as increased colony-forming cells in blood and spleen compared with saline-injected unirradiated controls. The irradiated mice showed markedly inhibited or absent mobilization regardless of the part of the body irradiated. To investigate the mechanism of radiation-induced mobilization inhibition, heparinized plasma was obtained from mice whose lower bodies were irradiated with 2 Gy 18 h previously, and 0.5 ml was injected i.v. into intact mice 10 min before they received 15 μg/kg G-CSF and 500 U/kg EPO. Unlike mice that received G-CSF + EPO only and showed mobilization of progenitors from marrow to spleen, recipients of plasma from irradiated mice before and after cytokine administration showed significantly reduced mobilization of progenitors. Thus, radiation-induced inhibition of stem cell mobilization is mediated by an unidentified circulating factor.

Original languageEnglish (US)
Pages (from-to)343-349
Number of pages7
JournalJournal of Hematotherapy and Stem Cell Research
Volume7
Issue number4
StatePublished - Aug 1 1998

Fingerprint

Blood Cells
Stem Cells
Radiation
Cytokines
Granulocyte Colony-Stimulating Factor
Erythropoietin
Hematopoietic Stem Cell Mobilization
Spleen
Radiotherapy
Drug Therapy
Autografts
Human Body
Allografts
Lower Extremity
Intercellular Signaling Peptides and Proteins
Bone Marrow
Injections

ASJC Scopus subject areas

  • Immunology
  • Hematology

Cite this

Concurrent partial body radiation prevents cytokine mobilization of blood progenitor cells : An effect mediated by a circulating factor. / Sharp, John G; Kessinger, A.; Clausen, S. R.; Mann, S. L.; O'Kane-Murphy, B.

In: Journal of Hematotherapy and Stem Cell Research, Vol. 7, No. 4, 01.08.1998, p. 343-349.

Research output: Contribution to journalArticle

@article{4a043da397d746bc96ea5890503288a2,
title = "Concurrent partial body radiation prevents cytokine mobilization of blood progenitor cells: An effect mediated by a circulating factor",
abstract = "Mobilization of stem and progenitor cells into blood, which facilitates the collection of blood-derived autograft and allograft products, can be accomplished with administration of myelosuppressive chemotherapy, hematopoietic growth factors, or both. Autologous donor indifference to mobilization attempts has been correlated with prior administration of chemotherapy and radiation therapy. To investigate whether concurrent administration of radiation therapy inhibits mobilization, five daily injections of a potent combination of mobilizing cytokines, 500 U/kg erythropoietin (EPO) plus 15 μg/kg G-CSF, were administered each morning to Balb/c mice. Each afternoon, a 2 Gy fraction of Co-60 radiation was administered to either the lower limb or the upper or lower hemibody. Each day, mice were necropsied, and blood stem cell mobilization was determined by assaying the number of hematopoietic colony-forming cells in the blood and in the spleen. Unirradiated cytokine-injected mice showed a significant mobilization effect evident as increased colony-forming cells in blood and spleen compared with saline-injected unirradiated controls. The irradiated mice showed markedly inhibited or absent mobilization regardless of the part of the body irradiated. To investigate the mechanism of radiation-induced mobilization inhibition, heparinized plasma was obtained from mice whose lower bodies were irradiated with 2 Gy 18 h previously, and 0.5 ml was injected i.v. into intact mice 10 min before they received 15 μg/kg G-CSF and 500 U/kg EPO. Unlike mice that received G-CSF + EPO only and showed mobilization of progenitors from marrow to spleen, recipients of plasma from irradiated mice before and after cytokine administration showed significantly reduced mobilization of progenitors. Thus, radiation-induced inhibition of stem cell mobilization is mediated by an unidentified circulating factor.",
author = "Sharp, {John G} and A. Kessinger and Clausen, {S. R.} and Mann, {S. L.} and B. O'Kane-Murphy",
year = "1998",
month = "8",
day = "1",
language = "English (US)",
volume = "7",
pages = "343--349",
journal = "Stem Cells and Development",
issn = "1547-3287",
publisher = "Mary Ann Liebert Inc.",
number = "4",

}

TY - JOUR

T1 - Concurrent partial body radiation prevents cytokine mobilization of blood progenitor cells

T2 - An effect mediated by a circulating factor

AU - Sharp, John G

AU - Kessinger, A.

AU - Clausen, S. R.

AU - Mann, S. L.

AU - O'Kane-Murphy, B.

PY - 1998/8/1

Y1 - 1998/8/1

N2 - Mobilization of stem and progenitor cells into blood, which facilitates the collection of blood-derived autograft and allograft products, can be accomplished with administration of myelosuppressive chemotherapy, hematopoietic growth factors, or both. Autologous donor indifference to mobilization attempts has been correlated with prior administration of chemotherapy and radiation therapy. To investigate whether concurrent administration of radiation therapy inhibits mobilization, five daily injections of a potent combination of mobilizing cytokines, 500 U/kg erythropoietin (EPO) plus 15 μg/kg G-CSF, were administered each morning to Balb/c mice. Each afternoon, a 2 Gy fraction of Co-60 radiation was administered to either the lower limb or the upper or lower hemibody. Each day, mice were necropsied, and blood stem cell mobilization was determined by assaying the number of hematopoietic colony-forming cells in the blood and in the spleen. Unirradiated cytokine-injected mice showed a significant mobilization effect evident as increased colony-forming cells in blood and spleen compared with saline-injected unirradiated controls. The irradiated mice showed markedly inhibited or absent mobilization regardless of the part of the body irradiated. To investigate the mechanism of radiation-induced mobilization inhibition, heparinized plasma was obtained from mice whose lower bodies were irradiated with 2 Gy 18 h previously, and 0.5 ml was injected i.v. into intact mice 10 min before they received 15 μg/kg G-CSF and 500 U/kg EPO. Unlike mice that received G-CSF + EPO only and showed mobilization of progenitors from marrow to spleen, recipients of plasma from irradiated mice before and after cytokine administration showed significantly reduced mobilization of progenitors. Thus, radiation-induced inhibition of stem cell mobilization is mediated by an unidentified circulating factor.

AB - Mobilization of stem and progenitor cells into blood, which facilitates the collection of blood-derived autograft and allograft products, can be accomplished with administration of myelosuppressive chemotherapy, hematopoietic growth factors, or both. Autologous donor indifference to mobilization attempts has been correlated with prior administration of chemotherapy and radiation therapy. To investigate whether concurrent administration of radiation therapy inhibits mobilization, five daily injections of a potent combination of mobilizing cytokines, 500 U/kg erythropoietin (EPO) plus 15 μg/kg G-CSF, were administered each morning to Balb/c mice. Each afternoon, a 2 Gy fraction of Co-60 radiation was administered to either the lower limb or the upper or lower hemibody. Each day, mice were necropsied, and blood stem cell mobilization was determined by assaying the number of hematopoietic colony-forming cells in the blood and in the spleen. Unirradiated cytokine-injected mice showed a significant mobilization effect evident as increased colony-forming cells in blood and spleen compared with saline-injected unirradiated controls. The irradiated mice showed markedly inhibited or absent mobilization regardless of the part of the body irradiated. To investigate the mechanism of radiation-induced mobilization inhibition, heparinized plasma was obtained from mice whose lower bodies were irradiated with 2 Gy 18 h previously, and 0.5 ml was injected i.v. into intact mice 10 min before they received 15 μg/kg G-CSF and 500 U/kg EPO. Unlike mice that received G-CSF + EPO only and showed mobilization of progenitors from marrow to spleen, recipients of plasma from irradiated mice before and after cytokine administration showed significantly reduced mobilization of progenitors. Thus, radiation-induced inhibition of stem cell mobilization is mediated by an unidentified circulating factor.

UR - http://www.scopus.com/inward/record.url?scp=0031667168&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031667168&partnerID=8YFLogxK

M3 - Article

C2 - 9735865

AN - SCOPUS:0031667168

VL - 7

SP - 343

EP - 349

JO - Stem Cells and Development

JF - Stem Cells and Development

SN - 1547-3287

IS - 4

ER -