title: 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.
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.
authors.affiliation: Department of Medicine, University of Minnesota, Minneapolis 55455, USA.
authors.forename: R
authors.initials: R
authors.lastname: Bhatia
authors.forename: P B
authors.initials: PB
authors.lastname: McGlave
authors.forename: C M
authors.initials: CM
authors.lastname: Verfaillie
mesh_terms: D000273:Adipose Tissue / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D001853:Bone Marrow / Q000187:drug effects*; D001854:Bone Marrow Cells; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D054407:Chemokine CCL4; D003238:Connective Tissue / Q000187:drug effects* / Q000378:metabolism; D003239:Connective Tissue Cells; D016207:Cytokines / Q000096:biosynthesis / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D006801:Humans; D019012:Integrin beta1; D016023:Integrins / Q000502:physiology*; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology*; D015466:Leukemia, Myeloid, Chronic-Phase / Q000473:pathology*; D019402:Macrophage Inflammatory Proteins; D015846:Monokines / Q000096:biosynthesis / Q000502:physiology*; D014411:Neoplastic Stem Cells / Q000502:physiology*; D011994:Recombinant Proteins
chemical_list: D054407:Chemokine CCL4; D016207:Cytokines; D019012:Integrin beta1; D016023:Integrins; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D019402:Macrophage Inflammatory Proteins; D015846:Monokines; D011994:Recombinant Proteins