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PMID: 7543495 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Treatment of marrow stroma with interferon-alpha restores normal beta 1 integrin-dependent adhesion of chronic myelogenous leukemia hematopoietic progenitors. Role of MIP-1 alpha.

The Journal of clinical investigation ·Vol. 96 ·No. 2 ·1995-08-00 ·Pages 931-9

Bhatia R, McGlave PB, Verfaillie CM

Abstract

The mechanisms by which interferon-alpha (IFN-alpha) restores normal hematopoiesis in chronic myelogenous leukemia (CML) are not well understood. We have recently demonstrated that IFN-alpha acts directly on CML hematopoietic progenitors to restore their adhesion to marrow stroma by modulating beta 1 integrin receptor function. In the present study we examined the effect of IFN-alpha treatment of marrow stroma on subsequent adhesion of CML progenitors. Stromal layers were preincubated with IFN-alpha (10,000 microns/ml) for 48 h. Subsequent coincubation with CML progenitors for 2 h resulted in significantly increased adhesion of CML progenitors. We demonstrated that alpha 4 beta 1 and alpha 5 beta 1 integrin receptors were involved in the enhanced adhesion of CML progenitors, suggesting that IFN-alpha-treated stroma can upregulate CML integrin function. This effect is due, at least in part, to IFN-alpha-induced increased stromal production of the chemokine macrophage inflammatory protein-1 alpha (MIP-1 alpha), which upregulates beta 1 integrin-dependent adhesion of CML progenitors to stroma. Thus, IFN-alpha treatment of marrow stroma restores beta 1 integrin-dependent adhesion of CML progenitors, at least in part through induction of MIP-1 alpha production. These observations provide further insights into mechanisms by which IFN-alpha may restore normal hematopoiesis in CML.

MeSH Terms
Adipose Tissue/cytology,drug effects,metabolism Bone Marrow/drug effects Bone Marrow Cells Cell Adhesion/drug effects Cells, Cultured Chemokine CCL4 Connective Tissue/drug effects,metabolism Connective Tissue Cells Cytokines/biosynthesis,physiology Hematopoietic Stem Cells/physiology Humans Integrin beta1 Integrins/physiology Interferon alpha-2 Interferon-alpha/pharmacology Leukemia, Myeloid, Chronic-Phase/pathology Macrophage Inflammatory Proteins Monokines/biosynthesis,physiology Neoplastic Stem Cells/physiology Recombinant Proteins
Chemicals
Chemokine CCL4 Cytokines Integrin beta1 Integrins Interferon alpha-2 Interferon-alpha Macrophage Inflammatory Proteins Monokines Recombinant Proteins
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Bhatia R
Department of Medicine, University of Minnesota, Minneapolis 55455, USA.
McGlave P B
Verfaillie C M
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI118141
Published
1995-08-00
Pages
931-9
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC185281
Subset
IM
Grants
NCI NIH HHS · R01-CA-4581401 · United States
NHLBI NIH HHS · R01-HL4993001 · United States
NHLBI NIH HHS · R01-HO5403901 · United States
External Links
PubMed source DOI: 10.1172/JCI118141 PMC Full Text View journal details
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