Influence of interleukin-3 and other growth factors on alpha4beta1 integrin-mediated adhesion and migration of human hematopoietic progenitor cells.

2.50
Hdl Handle:
http://hdl.handle.net/10541/94931
Title:
Influence of interleukin-3 and other growth factors on alpha4beta1 integrin-mediated adhesion and migration of human hematopoietic progenitor cells.
Authors:
Schofield, Karen P; Rushton, Graham; Humphries, Martin J; Dexter, T Michael; Gallagher, John T
Abstract:
The mechanisms by which hematopoietic progenitor cells are normally anchored in stromal niches and yet can be mobilized by specific growth factors are poorly understood. It is likely, however, that integrins and their extracellular matrix (ECM) ligands play a key role in this process, and recent evidence suggests that integrin function is modulated by signals originating from activated growth factor receptors. We have now examined this further by studying the role of growth factors on alpha4beta1 integrin-mediated adhesion of human CD34+ hematopoietic progenitor cells to specific recombinant fibronectin fragments coated onto tissue culture dishes. Cells were prepared from cord blood and peripheral blood harvests. During a 30-minute adhesion assay a mean of 74% of CD34 cells attached to the so-called H120 fragment of fibronectin, which contains the strongest alpha4beta1 integrin-binding sequence. The level of cell adhesion was significantly reduced by low concentrations of interleukin-3 (IL-3) (2.5 to 10 ng/mL), whereas stem cell factor (SCF) and granulocyte colony-stimulating factor (G-CSF) at these concentrations did not affect adherence of the cells. Migratory behavior of CD34 cells was examined using fibronectin fragments adsorbed onto a Transwell filter. The H120 fragment supported much higher levels of cell migration than the H0 fragment of fibronectin, which contains a weak alpha4beta1 integrin binding sequence. Over a 16-hour assay, migration of peripheral blood progenitor cells was increased slightly by SCF and by G-CSF. However, a marked stimulation was observed with IL-3, which significantly increased migration. Similar effects were noted with cord blood cells, although a small proportion of cells were able to migrate in the absence of growth factors. These results indicate that there is a highly selective and functional link between the alpha4beta1 integrin and IL-3/IL-3-receptor that could affect the position of stem and progenitor cells in the marrow stroma and influence their growth and development.
Affiliation:
Department of Medical Oncology, Paterson Institute, Manchester, UK.
Citation:
Influence of interleukin-3 and other growth factors on alpha4beta1 integrin-mediated adhesion and migration of human hematopoietic progenitor cells. 1997, 90 (5):1858-66 Blood
Journal:
Blood
Issue Date:
1-Sep-1997
URI:
http://hdl.handle.net/10541/94931
PubMed ID:
9292518
Type:
Article
Language:
en
ISSN:
0006-4971
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorSchofield, Karen Pen
dc.contributor.authorRushton, Grahamen
dc.contributor.authorHumphries, Martin Jen
dc.contributor.authorDexter, T Michaelen
dc.contributor.authorGallagher, John Ten
dc.date.accessioned2010-03-24T16:23:13Z-
dc.date.available2010-03-24T16:23:13Z-
dc.date.issued1997-09-01-
dc.identifier.citationInfluence of interleukin-3 and other growth factors on alpha4beta1 integrin-mediated adhesion and migration of human hematopoietic progenitor cells. 1997, 90 (5):1858-66 Blooden
dc.identifier.issn0006-4971-
dc.identifier.pmid9292518-
dc.identifier.urihttp://hdl.handle.net/10541/94931-
dc.description.abstractThe mechanisms by which hematopoietic progenitor cells are normally anchored in stromal niches and yet can be mobilized by specific growth factors are poorly understood. It is likely, however, that integrins and their extracellular matrix (ECM) ligands play a key role in this process, and recent evidence suggests that integrin function is modulated by signals originating from activated growth factor receptors. We have now examined this further by studying the role of growth factors on alpha4beta1 integrin-mediated adhesion of human CD34+ hematopoietic progenitor cells to specific recombinant fibronectin fragments coated onto tissue culture dishes. Cells were prepared from cord blood and peripheral blood harvests. During a 30-minute adhesion assay a mean of 74% of CD34 cells attached to the so-called H120 fragment of fibronectin, which contains the strongest alpha4beta1 integrin-binding sequence. The level of cell adhesion was significantly reduced by low concentrations of interleukin-3 (IL-3) (2.5 to 10 ng/mL), whereas stem cell factor (SCF) and granulocyte colony-stimulating factor (G-CSF) at these concentrations did not affect adherence of the cells. Migratory behavior of CD34 cells was examined using fibronectin fragments adsorbed onto a Transwell filter. The H120 fragment supported much higher levels of cell migration than the H0 fragment of fibronectin, which contains a weak alpha4beta1 integrin binding sequence. Over a 16-hour assay, migration of peripheral blood progenitor cells was increased slightly by SCF and by G-CSF. However, a marked stimulation was observed with IL-3, which significantly increased migration. Similar effects were noted with cord blood cells, although a small proportion of cells were able to migrate in the absence of growth factors. These results indicate that there is a highly selective and functional link between the alpha4beta1 integrin and IL-3/IL-3-receptor that could affect the position of stem and progenitor cells in the marrow stroma and influence their growth and development.en
dc.language.isoenen
dc.subjectHaematopoietic Stem Cellsen
dc.subject.meshAntigens, CD34-
dc.subject.meshCell Adhesion-
dc.subject.meshCell Movement-
dc.subject.meshCells, Cultured-
dc.subject.meshGranulocyte Colony-Stimulating Factor-
dc.subject.meshHematopoietic Stem Cells-
dc.subject.meshHumans-
dc.subject.meshIntegrin alpha4beta1-
dc.subject.meshIntegrins-
dc.subject.meshInterleukin-3-
dc.subject.meshMutation-
dc.subject.meshReceptors, Lymphocyte Homing-
dc.subject.meshStem Cell Factor-
dc.titleInfluence of interleukin-3 and other growth factors on alpha4beta1 integrin-mediated adhesion and migration of human hematopoietic progenitor cells.en
dc.typeArticleen
dc.contributor.departmentDepartment of Medical Oncology, Paterson Institute, Manchester, UK.en
dc.identifier.journalBlooden
All Items in Christie are protected by copyright, with all rights reserved, unless otherwise indicated.